Distinguishing soft-tissue hemangiomas from vascular malformations using technetium-labeled red blood cell scintigraphy.

Soft-tissue vascular lesions in children can be classified as either hemangiomas or vascular malformations. The distinction between the two has important prognostic and therapeutic implications. Over the past 8 years, we have evaluated 64 vascular lesions with the technetium-labeled red blood cell (Tc-RBC) scan. Twenty-eight lesions imaged as hemangiomas with intense focal uniform uptake. This diagnosis was confirmed in 27 lesions, or 96 percent. Thirty-six lesions imaged as vascular malformations with abnormal vessels or diffusely increased activity. This diagnosis was confirmed in 35 lesions, or 97 percent. Overall, the Tc-RBC scan was 97 percent accurate in distinguishing hemangiomas from vascular malformations. It is particularly useful when the clinical diagnosis of the lesion may not be evident. Not only can biopsy be avoided, but parents can be reassured at an earlier age and given accurate information regarding prognosis.     

COMMON LESIONS OF THE URETHRA IN WOMEN

Urethral disease in women and girls often is overlooked. As the urine may seem to be normal as determined by repeated urinalysis, the symptoms—urinary frequency and burning—may be attributed entirely to other pelvic disease or to functional disorder. Since erroneous diagnosis may lead to unnecessary procedures or to neglect of treatment with consequent development of severe disease in the kidneys or ureters, it is important to consider urethral lesions as a possible cause in any case of abdominal discomfort in women.The most common lesions of the urethra in women are urethritis, stricture, caruncle, inflammatory polyps and cysts, prolapse of the urethra, and diverticulum. In some cases diagnosis can be made simply on the basis of inspection and palpation. In others more extensive diagnostic procedures must be carried out in order that treatment may be definitive.The methods of treatment, varying with the nature of the lesion, are outlined herein.     

PARTURIENT PERINEORRHAPHY

In the light of improved means of combating infection, better and safer anesthesia, the ready availability of blood transfusion, and less traumatic delivery, reasons formerly advanced in opposition to operations at the time of parturition for repair of preexisting lesions of the pelvic floor are now less formidable than they were in the past.Such operations now can be carried out quickly and safely with considerable benefit in terms of immediate comfort and well-being of the patient, prevention of later development of more serious lesions, and savings in cost of hospitalization.In a series of more than 300 patients so operated upon—the technique used is described herein—none died, and in a review of the records many advantages of operation immediately after delivery, as compared with long delay of needed repair, were noted.     

A TEST FOR EVALUATING PEDAL GANGRENOUS LESIONS—Observation of Elevation Reactive Hyperemia as a Gauge of Blood Supply

Estimating the development of collateral circulation in peripheral vascular diseases is simplified by the use of an easy test—which can be done in an office—in which reactive hyperemia is observed in an extremity as it is gradually lowered after a period of elevation.The lower limits of filling pressures necessary to allow spontaneous healing of necrotic lesions under the conditions described seem to be in the range 35 cm. above the heart. Similarly the lower limit for the successful performance of amputations at the level of the forefoot or toes seems to be about 45 cm.As a result of over a thousand observations in a period of over five years, it is believed that the test provides in a few minutes a visual and reproducible picture of the filling pressures in the distal portions of the extremity which is useful in the determination of prognosis and the selection of treatment of gangrenous lesions of the foot.     

The Association between Meteorological Parameters and Aneurysmal Subarachnoid Hemorrhage: A Nationwide Analysis

Prior research has suggested that regional weather patterns impact the risk of rupture of cerebral aneurysms, but the findings in the literature have been inconsistent. Furthermore, no nationwide analysis to date has examined the association between meteorological factors and the post-procedural outcomes of patients after the treatment for ruptured cerebral aneurysms. The purpose of this study was to use a nationwide sample to analyze the association between specific meteorological parameters—temperature, precipitation, sunlight, and humidity—and hospital admission rate for and outcome after aneurysmal subarachnoid hemorrhage. Patients were identified using the Nationwide Inpatient Sample (2001–2010): Those with an ICD-9 diagnosis code for subarachnoid hemorrhage and a procedural code for aneurysm repair were included. Climate data were obtained from the State of the Climate Report 2010 released by the National Climatic Data Center. Multivariate regression models were constructed to analyze the association between average state monthly temperature, precipitation, and percent possible sunlight, as well as relative morning humidity and both monthly hospital admission rate, adjusted for annual state population in millions, and in-hospital mortality. 16,970 admissions were included from 723 hospitals across 41 states. Decreased daily sunlight and lower relative humidity were associated with an increased rate of admission for ruptured cerebral aneurysms (p<0.001), but had no association with differential inpatient mortality. No significant changes in these observed associations were seen when multivariate analyses were constructed. This is the first nationwide study to suggest that decreased sunlight and lower relative humidity are associated with admission for ruptured cerebral aneurysms. While it has been postulated that external atmospheric factors may cause hormonal and homeostatic changes that impact the risk of rupture of cerebral aneurysms, additional research is needed to confirm and further understand these relationships.     

Fine needle aspiration cytology of intraoral epithelioid hemangioma. A report of two cases

BACKGROUND: Epithelioid hemangioma (EH) is an uncommon, benign, vascular lesion of unknown etiology. The clinical differential diagnosis is broad and includes both epithelial and vascular neoplasms. In contrast to the histopathology of this lesion, the cytopathology, as obtained by fine needle aspiration biopsy (FNAB), has been described only once before. CASES: Two cases of EH of the oral cavity were evaluated by FNAB. The first case included histologic follow-up, while the second included immunohistochemical analysis of the aspirate material (cell block). The smear characteristics included cohesive epithelioid cells with moderate cytoplasm, ovoid nuclei and small nucleoli that formed occasional abortive vascular channels as well as spindle cell groups and a few larger cells with pleomorphic nuclei and irregular nuclear contours against a largely bloody background. Immunohistochemical staining for CD34 and factor VIII-related antigen confirmed the endothelial nature of these proliferations. CONCLUSION: The cytomorphology, an endothelial immunophenotype, and the appropriate clinical presentation should permit diagnostic consideration of EH in the differential diagnosis of an endothelial lesion.     

Testing Foundations of Biological Scaling Theory Using Automated Measurements of Vascular Networks

Scientists have long sought to understand how vascular networks supply blood and oxygen to cells throughout the body. Recent work focuses on principles that constrain how vessel size changes through branching generations from the aorta to capillaries and uses scaling exponents to quantify these changes. Prominent scaling theories predict that combinations of these exponents explain how metabolic, growth, and other biological rates vary with body size. Nevertheless, direct measurements of individual vessel segments have been limited because existing techniques for measuring vasculature are invasive, time consuming, and technically difficult. We developed software that extracts the length, radius, and connectivity of in vivo vessels from contrast-enhanced 3D Magnetic Resonance Angiography. Using data from 20 human subjects, we calculated scaling exponents by four methods—two derived from local properties of branching junctions and two from whole-network properties. Although these methods are often used interchangeably in the literature, we do not find general agreement between these methods, particularly for vessel lengths. Measurements for length of vessels also diverge from theoretical values, but those for radius show stronger agreement. Our results demonstrate that vascular network models cannot ignore certain complexities of real vascular systems and indicate the need to discover new principles regarding vessel lengths.     

Human abasic endonuclease action on multilesion abasic clusters: implications for radiation-induced biological damage

Clustered damages—two or more closely opposed abasic sites, oxidized bases or strand breaks—are induced in DNA by ionizing radiation and by some radiomimetic drugs. They are potentially mutagenic or lethal. High complexity, multilesion clusters (three or more lesions) are hypothesized as repair-resistant and responsible for the greater biological damage induced by high linear energy transfer radiation (e.g. charged particles) than by low linear energy transfer X- or γ-rays. We tested this hypothesis by assessing human abasic endonuclease Ape1 activity on two- and multiple-lesion abasic clusters. We constructed cluster-containing oligonucleotides using a central variable cassette with abasic site(s) at specific locations, and 5′ and 3′ terminal segments tagged with visually distinctive fluorophores. The results indicate that in two- or multiple-lesion clusters, the spatial arrangement of uni-sided positive [in which the opposing strand lesion(s) is 3′ to the base opposite the reference lesion)] or negative polarity [opposing strand lesion(s) 5′ to the base opposite the reference lesion] abasic clusters is key in determining Ape1 cleavage efficiency. However, no bipolar clusters (minimally three-lesions) were good Ape1 substrates. The data suggest an underlying molecular mechanism for the higher levels of biological damage associated with agents producing complex clusters: the induction of highly repair-resistant bipolar clusters.     

DNA lesion identity drives choice of damage tolerance pathway in murine cell chromosomes

DNA-damage tolerance (DDT) via translesion DNA synthesis (TLS) or homology-dependent repair (HDR) functions to bypass DNA lesions encountered during replication, and is critical for maintaining genome stability. Here, we present piggyBlock, a new chromosomal assay that, using piggyBac transposition of DNA containing a known lesion, measures the division of labor between the two DDT pathways. We show that in the absence of DNA damage response, tolerance of the most common sunlight-induced DNA lesion, TT-CPD, is achieved by TLS in mouse embryo fibroblasts. Meanwhile, BP-G, a major smoke-induced DNA lesion, is bypassed primarily by HDR, providing the first evidence for this mechanism being the main tolerance pathway for a biologically important lesion in a mammalian genome. We also show that, far from being a last-resort strategy as it is sometimes portrayed, TLS operates alongside nucleotide excision repair, handling 40% of TT-CPDs in repair-proficient cells. Finally, DDT acts in mouse embryonic stem cells, exhibiting the same pattern—mutagenic TLS included—despite the risk of propagating mutations along all cell lineages. The new method highlights the importance of HDR, and provides an effective tool for studying DDT in mammalian cells.     

Application of Dual Phase Imaging of 11C-Acetate Positron Emission Tomography on Differential Diagnosis of Small Hepatic Lesions

Objective

Previously we observed that dual phase ¹¹C-acetate positron emission tomography (AC-PET) could be employed for differential diagnosis of liver malignancies. In this study, we prospectively evaluated the effect of dual phase AC-PET on differential diagnosis of primary hepatic lesions of 1–3 cm in size.

Methods

33 patients having primary hepatic lesions with size of 1–3 cm in diameter undertook dual phase AC-PET scans. Procedure included an early upper-abdomen scan immediately after tracer injection and a conventional scan in 11–18 min. The standardized uptake value (SUV) was calculated for tumor (SUVT) and normal tissue (SUVB), from which ¹¹C-acetate uptake ratio (as lesion against normal liver tissue, SUVT/SUVB) in early imaging (R1), conventional imaging (R2), and variance between R2 and R1 (ΔR) were derived. Diagnoses based on AC-PET data and histology were compared. Statistical analysis was performed with SPSS 19.0.

Results

20 patients were found to have HCC and 13 patients had benign tumors. Using ΔR>0 as criterion for malignancy, the accuracy and specificity were significantly increased comparing with conventional method. The area under ROC curve (AUC) for R1, R2, and ΔR were 0.417, 0.683 and 0.831 respectively. Differential diagnosis between well-differentiated HCCs and benign lesions of FNHs and hemangiomas achieved 100% correct. Strong positive correlation was also found between R1 and R2 in HCC (r² = 0.55, P<0.001).

Conclusions

Dual phase AC-PET scan is a useful procedure for differential diagnosis of well-differentiated hepatocellular carcinoma and benign lesions. The dynamic changes of ¹¹C-acetate uptake in dual phase imaging provided key information for final diagnosis.     

RNA length has a non-trivial effect in the stability of biomolecular condensates formed by RNA-binding proteins

Biomolecular condensates formed via liquid–liquid phase separation (LLPS) play a crucial role in the spatiotemporal organization of the cell material. Nucleic acids can act as critical modulators in the stability of these protein condensates. To unveil the role of RNA length in regulating the stability of RNA binding protein (RBP) condensates, we present a multiscale computational strategy that exploits the advantages of a sequence-dependent coarse-grained representation of proteins and a minimal coarse-grained model wherein proteins are described as patchy colloids. We find that for a constant nucleotide/protein ratio, the protein fused in sarcoma (FUS), which can phase separate on its own—i.e., via homotypic interactions—only exhibits a mild dependency on the RNA strand length. In contrast, the 25-repeat proline-arginine peptide (PR₂₅), which does not undergo LLPS on its own at physiological conditions but instead exhibits complex coacervation with RNA—i.e., via heterotypic interactions—shows a strong dependence on the length of the RNA strands. Our minimal patchy particle simulations suggest that the strikingly different effect of RNA length on homotypic LLPS versus RBP–RNA complex coacervation is general. Phase separation is RNA-length dependent whenever the relative contribution of heterotypic interactions sustaining LLPS is comparable or higher than those stemming from protein homotypic interactions. Taken together, our results contribute to illuminate the intricate physicochemical mechanisms that influence the stability of RBP condensates through RNA inclusion.     

Primary amoebic meningoencephalitis in Britain

Primary amoebic meningoencephalitis is caused by amoebae of the genera Naegleria and Hartmannella (Acanthamoeba), which ordinarily are free-living saprophytes. The infection may be acquired from fresh water—for example, while bathing—the amoebae invading the nasal mucosa and reaching the meninges and brain along the olfactory nerve filaments. The disease is designated “primary” to distinguish it from meningocerebral infection caused by the parasitic amoebae, particularly Entamoeba histolytica, which invade the central nervous system only as a result of dissemination in the blood stream from lesions in other parts of the body.During histological reappraisal of old specimens in a medical museum in London an instance of amoebic meningoencephalitis histologically indistinguishable from the published cases has been found. The specimen dates from 1909. The patient was said to be from Essex. What may have been another case, seen in Northern Ireland in 1937, is also described briefly. These observations may indicate that this disease occurs in the British Isles.Primary amoebic meningoencephalitis should be considered in the differential diagnosis of every case of acute meningitis.     

Comparison of Birth Weight/Gestation Distribution in Cases of Stillbirth and Neonatal Death According to Lesions Found at Necropsy

The birth weight/gestation distribution of a large series of cases of perinatal death has been analysed according to the lesion (or lesions) present at necropsy. Among the lesions associated with low gestation babies dying with hyaline membranes have a much higher mean birth weight for gestation than either the babies with intraventricular haemorrhage or “no cause found.” Among infants dying of intrapartum asphyxia or cerebral birth trauma it was found that those who were stillborn with trauma had, at term, a significantly higher mean birth weight than the control livebirths, and that, at all gestations, the stillbirths with trauma were, on average, heavier than the babies dying neonatally with this lesion. Cases of intrapartum asphyxia were smaller than the stillbirths with trauma, but those dying during the second stage of labour were larger than those dying during the first stage.Cases of intrauterine pneumonia—that is, stillbirths and first-day deaths—were also shown to be larger for length of gestation than cases of extrauterine pneumonia—that is, deaths between the second and the 28th day. The cases with haemorrhagic pneumonia, however, were, at least at term, smaller than the cases of extrauterine pneumonia, and cases of massive pulmonary haemorrhage showed evidence of growth retardation at all gestations.     

THE ROLE OF THE CONNECTIVE TISSUE GROUND SUBSTANCES (MUCOPOLYSACCHARIDES) IN ALLERGIC INJURY

The basic histologic reactions of the classic allergic diseases and of several systemic diseases in which allergic mechanisms appear to operate are described and illustrated. Particular attention is drawn to the ground substances—mucopolysaccharides—which constitute important elements of connective tissue and vascular structure. The intimate locus of the allergic reaction appears to be in and to involve a swelling of such substances. It is suggested that antibodies (and possibly antigens) may be attached to these mucinous ground substances of the connective tissues.     

The Role of Percutaneous Lung Biopsy in the Workup of a Solitary Pulmonary Nodule

As the technique of percutaneous lung biopsy continues to evolve, it offers an increasingly accurate method of establishing the malignancy or benignity of a solitary pulmonary nodule. There are relatively few contraindications to the procedure, and the complications—primarily pneumothorax and hemoptysis—generally resolve without therapy. Transthoracic needle aspiration has an important role in the workup for a “coin lesion.” Other elements of the diagnostic workup—particularly the history, a chest roentgenogram, computed tomography, sputum cytology, and transbronchial brush biopsy—may either add to or substitute for a transthoracic needle aspiration biopsy. An algorithm can be used to guide the diagnostic approach to a solitary pulmonary nodule.     

Multiscale modeling of tumor growth and angiogenesis: Evaluation of tumor-targeted therapy

The dynamics of tumor growth and associated events cover multiple time and spatial scales, generally including extracellular, cellular and intracellular modifications. The main goal of this study is to model the biological and physical behavior of tumor evolution in presence of normal healthy tissue, considering a variety of events involved in the process. These include hyper and hypoactivation of signaling pathways during tumor growth, vessels’ growth, intratumoral vascularization and competition of cancer cells with healthy host tissue. The work addresses two distinctive phases in tumor development—the avascular and vascular phases—and in each stage two cases are considered—with and without normal healthy cells. The tumor growth rate increases considerably as closed vessel loops (anastomoses) form around the tumor cells resulting from tumor induced vascularization. When taking into account the host tissue around the tumor, the results show that competition between normal cells and cancer cells leads to the formation of a hypoxic tumor core within a relatively short period of time. Moreover, a dense intratumoral vascular network is formed throughout the entire lesion as a sign of a high malignancy grade, which is consistent with reported experimental data for several types of solid carcinomas. In comparison with other mathematical models of tumor development, in this work we introduce a multiscale simulation that models the cellular interactions and cell behavior as a consequence of the activation of oncogenes and deactivation of gene signaling pathways within each cell. Simulating a therapy that blocks relevant signaling pathways results in the prevention of further tumor growth and leads to an expressive decrease in its size (82% in the simulation).     

SURGICAL PRINCIPLES OF INCISING THE RENAL PARENCHYMA

Attention, at nephrotomy, to the anatomy of the kidney will guide incision into a less vascular area and will result in less destruction of tissue. Complete exposure and gentleness of control of the renal pedicle are mandatory. Conservative surgery—removing renal lesions and preserving the remaining functioning tissue — is successful when the proper techniques of incision and hemostasis are employed. With proper drainage and control of infection, nephrostomy is not necessary. Three illustrative cases are presented.Full use of the operating room x-ray machine is helpful. Mattress sutures in the plane of the arteries is the commonest method of parenchymal hemostasis. Although helpful, Gelfoam® and Oxycel® probably predispose to infection which is the commonest cause of secondary hemorrhage.     

Adrenocortical Neoplasms With Myelolipomatous and Lipomatous Metaplasia: Report of 3 Cases

ObjectiveTo present pathologic and radiographic features of 3 patients with adrenocortical neoplasms—2 with uncertain malignant potential and 1 adenoma with areas of myelolipomatous and lipomatous metaplasia.MethodsWe describe 3 patients who had adrenocortical neoplasms with foci of myelolipomatous and lipomatous metaplasia. For each patient, the clinical and pathologic data are reviewed.ResultsAll 3 patients were women, with a mean age at presentation of 58 years. The lesion size averaged 6.8 cm (range, 3.9 to 11.0), and the mean gland weight was 128.8 g (range, 32.5 to 249). Two patients showed imaging findings compatible with adrenal myelolipoma. Pathologically, 2 of the lesions were classified as adrenocortical neoplasms of uncertain malignant potential, and 1 lesion was classified as an adrenocortical adenoma. All 3 lesions contained myelolipomatous foci throughout the neoplasm, and 2 of the tumors contained several pure lipomatous foci.ConclusionAdrenocortical neoplasms, including those associated with an uncertain malignant potential, may be associated with areas of myelolipomatous and lipomatous metaplasia. Imaging studies may result in a false diagnosis of a benign adrenal myelolipoma and potential undertreatment in such patients. (Endocr Pract. 2009;15:128-133)     

CARCINOMA OF THE CERVIX

Studies by eminent surgeons to reevaluate the place of radical operations in the treatment of carcinoma of the cervix—now that extensive procedures have become less hazardous—apparently have led to confusion in some minds as to choice between surgical and radiation therapy. Pending outcome of the studies, general employment of surgical treatment is unwarranted. Radiation is the treatment of choice in most cases, particularly if the lesion is in an early stage, although radical operation is indicated in certain rare early cases in which delivery of an effective dose of radiation to involved areas is technically difficult. Elsewise it appears at present that operation should be used only in cases of stages III or IV carcinoma—in which results by either means of treatment are poor.One hundred and seven patients were treated with a combination of x-ray and radium irradiation. X-ray was used first to reduce the hazard of implanting the radium. The “five-year arrest” rates were as follows: For 22 patients with stage I lesion, 70 per cent; for 31 with stage II, 55.7 per cent; 33 with stage III, 39.7 per cent; 21 with stage IV, 0. Eighteen patients with diagnosis of carcinoma of the cervix who had had subtotal hysterectomy were treated. The stage of the disease could not be determined. In this group the five-year arrest rate was 52 per cent.