Circulatory and Respiratory Effects Evoked by Hypertonic Ventriculo-Cisternal Perfusion

The cerebral ventricular system of anesthetized dogs was perfused with synthetic isotonic CSF and, for 80 s intervals, with hypertonic CSF of various compositions. Hypertonic perfusion evoked centrally mediated marked increases in arterial blood pressure, heart rate, respiratory rate, and ventilation and, after some delay, an excitatory resembling arousal. The responses were coordinated in time with the induced CSF hypertonicity, graded in relation to its magnitude, and reversible on return to isotonicity. The effects, which seemed to be elicited from periventricular structures in the brain stem, were more pronounced and consistent when CSF hypertonicity was produced by adding NaCl or Na-lactate than monosacharides to the isotonic CSF solution. Analysis of the cardiovascular responses indicated that they were caused by increased sympathetic vasoconstrictor and cardiac accelerance fibre activity and by inhibition of vagal discharge to the heart. The described pattern of response much resembles that evoked by physical exercise, a state which might lead to osmolar changes in the brain and CSF of a similar kind to that in the present study as a consequence of the pronounced work-induced arterial hyperosmolality. It is suggested that such an osmotic mechanism might constitute a “metabolic link” in the centrally mediated circulatory and respiratory adjustments in exercise.     

‘Aging bull’

An old bull, it is said by those who know, can have his troubles. Included among these are vertebral osteosclerosis and ankylosing spondylosis; this stiffening up limits, rather than accentuates, the value and reproductive potential of a stud bull past his prime.Associated with these abnormalities, however- and not seen in age-matched cows of comparable breeds — are fascinating endocrine neoplasms suggestive of a pattern that could be productive as a model of human hereditary endocrine abnormalities.Adjacent to the thyroid gland in other vertebrates are ultimobranchial bodies that are incorporated into the lateral thyroid lobes in primates as the parafollicular ‘C cells’ of the thyroid. These are the cells in man that give rise to medullary thyroid cancer and are associated with calcitonin secretion, useful as a tumor marker.In aging bulls of whatever breed, nearly half exhibit abnormality of these ultimobranchial bodies: 20% show hyperplasia, and 30% have frank neoplasia. These ultimobranchial tumors appear in bulls passing 61/2 years in age, and are absent in young bulls and all cows of any age. Calcitonin can be demonstrated in the ultimobranchial tumors from bulls, and secretion is stimulated by calcium infusion, though serum calcium remains normal. The ultimobranchial tumors themselves can range from hyperplasia through adenoma to metastasizing carcinoma — in fact, representing one of the commoner cattle cancers. Parathyroid glands taken from bulls with these ultimobranchial tumors initially show evidence of inhibited secretory activity and morphologic atrophy, but later go on to develop hyperplasia and, eventually, autonomy.Cattle forage on calcium-rich diets. Bulls appear to respond to this calcium excess from the positive balance, but breeding cows have the unique calcium deficits of the high net loss of calcium through lactation and the large requirements of calcifying a fetal skeleton. Chronic stimulation of the APUD-derived ultimobranchial bodies by high calcium intake, not counterbalanced by calcium losses in the bulls, may account for the development over time of the ultimobranchial neoplasms.Further, a number of the bulls who have the ultimobranchial tumors are found to have multiple endocrine tumors in other glands — bilateral pheochromocytomas and pituitary acidophil adenomas.     

Are patients with chronic fatigue syndrome just ‘tired’ or also ‘sleepy’?

It is presently unclear whether chronic fatigue syndrome (CFS) patients exhibit daytime sleepiness in addition to fatigue. Both, fatigue, such as that seen in CFS patients, and excessive daytime sleepiness, such as in sleep apnea–hypopnea syndrome (SAHS), remain poorly understood. Both daytime conditions are generally related to unrefreshing sleep and show affective symptoms. This study’s objective was to contribute to the understanding of the relationship between fatigue and sleepiness in CFS patients not co‐morbid for primary sleep or psychiatric disorders. We compared 16 untreated CFS patients (mean age 32.8, all females) with 13 untreated SAHS (mean age 47.7, all females) patients and 12 healthy controls (mean age 32.2, all females). Objective sleepiness was measured using multiple sleep latency tests (MSLT). Subjective sleepiness and fatigue were assessed with the Epworth Sleepiness Scale and the Fatigue Severity Scale, respectively. Mean Sleep Latency (SL) on the MSLT was significantly shorter in SAHS patients than in CFS patients and CFS patients showed significantly shorter mean SL than matched controls but within normal range. Subjective sleepiness was greatest in SAHS patients and subjective fatigue was highest in CFS patients. Affective symptoms showed highest intensities in CFS patients. While higher than the control group on all measures, compared to SAHS, the CFS group had higher subjective fatigue and lower subjective and objective sleepiness. Despite possible overlap in symptoms and signs of both daytime conditions, our data indirectly support the clinical distinction between fatigue and sleepiness.     

‘Kir’‐ing thyrotoxic periodic paralysis

Mutations in potassium channel Kir2.6 cause susceptibility to thyrotoxic hypokalemic periodic paralysis Ryan et al. (2010) Cell 140:88–98.     

‘Entopy’: local allergy paradigm

Cite this as: D. G. Powe, A. J. Bonnin and N. S. Jones, Clinical & Experimental Allergy, 2010 (40) 987–997. Allergy is defined as an immediate hypersensitivity type I immunological disease, which can be IgE or non‐IgE driven, and in the latter case may be antibody or cell mediated. Atopy is a term used to describe individuals with a genetic predisposition for developing IgE‐mediated allergic disease. But more recently, it has become evident that IgE‐mediated disease can occur in non‐atopic subjects. While it is now generally accepted that mucosal local IgE has a role in the expression of atopic allergic disease, the concept of ‘local allergy’ in non‐atopic subjects has been proposed, with the term ‘entopy’ given to this condition. Although there is increasing evidence supporting this paradigm, entopy is only applicable to a proportion of non‐atopic patients, suggesting that other disease mechanisms exist to explain non‐atopic disease. This review considers the evidence for local mucosal allergy in atopic and non‐atopic individuals with an emphasis on diseases affecting the upper airways and eye. Furthermore, the diagnosis, treatment and relationship between local allergy and conventional (systemic) allergy are discussed, and alternative disease mechanisms predominantly involving antibodies or their sub‐components (free light chain Igs) are postulated to explain the ‘entopy’ paradigm. This review is intended to provide an improved understanding of the mechanisms and causes of local mucosal hypersensitivity.     

Lymphocyte ‘homing’ and chronic inflammation

Chronic inflammation is a response to prolonged exposure to injurious stimuli that harm and destroy tissues and promote lymphocyte infiltration into inflamed sites. Following progressive accumulation of lymphocytes, the histology of inflamed tissue begins to resemble that of peripheral lymphoid organs, which can be referred to as lymphoid neogenesis or formation of tertiary lymphoid tissues. Lymphocyte recruitment to inflamed tissues is also reminiscent of lymphocyte homing to peripheral lymphoid organs. In the latter, under physiological conditions, homing receptors expressed on lymphocytes adhere to vascular addressin expressed on high endothelial venules (HEVs), initiating a lymphocyte migration process composed of sequential adhesive interactions. Intriguingly, in chronic inflammation, HEV‐like vessels are induced de novo, despite the fact that the inflamed site is not originally lymphoid tissue, and these vessels contribute to lymphocyte recruitment in a manner similar to physiological lymphocyte homing. In this review, we first describe physiological lymphocyte homing mechanisms focusing on vascular addressins. We then describe HEV‐like vessel‐mediated pathogenesis seen in various chronic inflammatory disorders such as Helicobacter pylori gastritis, inflammatory bowel disease (IBD), autoimmune pancreatitis and sclerosing sialadenitis, as well as chronic inflammatory cell neoplasm MALT lymphoma, with reference to our work and that of others.     

‘Reverse wedge’ high tibial osteotomy

Five patients underwent a reverse wedge high tibial osteotomy for severe varus deformity of the knee. Four patients needed bone grafting for delayed union. All five patients had some loss of initial correction, with three partially reverting to the original varus deformity. This method of high tibial osteotomy is not recommended.     

Stabilization and surface modification of monoclonal antibodies by ‘bi-layer encagement’

A two step simple procedure for antibody stabilization in soluble form was developed. The antibody is first treated with low molecular weight polyaldehyde (polyglutaraldehyde). Following removal of non-bound polyaldehyde the antibody-polyaldehyde conjugate is crosslinked by polyamine (alkyl amine derivative of polyglutaraldehyde). Feasibility studies were successfully conducted employing monoclonal antibody raised against horseradish peroxidase as model system. The stabilized antibody preparation exhibited improved thermal stability, enhanced resistance to proteolytic digestion and higher ‘specific binding activity’ in ELISA test, without losing its capability to bind large antigen (enzyme) or being recognized by another antibody (goat anti-mouse IgG).     

Solid pseudopapillary tumor of the pancreas: ‘Experiences’ and ‘Lessons’ at a tertiary‐care oncology center

Solid pseudopapillary tumor of the pancreas (SPT) is a rare and fascinating entity of elusive histogenesis and unpredictable biology. It has a peculiar proclivity to afflict young females and involve the pancreatic body‐tail region. Cytology diagnosis of these rare neoplasms remains a challenge. We analyzed the cytology features of all SPT cases diagnosed on fine needle aspiration cytology (FNAC) from 2003 to 2009 along with their histopathology slides. Nineteen consecutive cases were diagnosed as SPT on FNAC. Fifteen out of nineteen cases were confirmed as true SPT on histopathology. Amongst the true SPT, all except one occurred in females. Age ranged from 14 to 50 years. Pseudopapillae bearing stout branches terminating in bulbous tips and enclosing transgressing vessels, separated from a collar of tumor cells by a clear zone of myxohyaline coat were pathognomonic of SPT. Singly dispersed monomorphic tumor cells with bland chromatin formed the second diagnostic component of SPT. Nuclear grooves and hyaline globules were in addition helpful in segregating SPT from its close differentials. In four cases diagnosed as SPT on FNAC, histopathology revealed a different final diagnosis (one case each of paraganglioma, extragastrointestinal stromal tumor, metastatic papillary renal cell carcinoma and inflammatory myofibroblastic tumor). Conversely, one case of SPT had been erroneously diagnosed as neuroendocrine tumor on FNAC. Six cases (40%) developed metastasis; commonest site being liver. In conclusion, cytology in conjunction with clinico‐radiologic findings plays a key role in making a correct diagnosis. Awareness of unique cytomorphological features is important in distinguishing this tumor from its diverse mimics. Diagn. Cytopathol. 2013. © 2012 Wiley Periodicals, Inc.