Aeromonas hydrophila and aspiration pneumonia: a diverse presentation

Although there are ever increasing reports of extraintestinal human infections caused by Aeromonads, in both immunocompromised and immunocompetent patients, respiratory tract infections remain uncommon. We describe a case of aspiration pneumonia in an immunocompetent patient with multiple sclerosis, caused by a community acquired, multidrug resistant strain of Aeromonas hydrophila sensitive only to meropenem. The case highlights the clinical significance of Aeromonas hydrophila as a respiratory pathogen, as well as the community origin of multidrug resistance and the utility of newer carbapenems in such cases.     

EGFR gene amplification in breast cancer: correlation with epidermal growth factor receptor mRNA and protein expression and HER-2 status and absence of EGFR-activating mutations.

The human epidermal growth factor receptor (HER) family of receptor tyrosine kinase has been extensively studied in breast cancer; however, systematic studies of EGFR gene amplification and protein overexpression in breast carcinoma are lacking. We studied EGFR gene amplification by chromogenic in situ hybridization (CISH) and protein expression by immunohistochemistry in 175 breast carcinomas, using tissue microarrays. Tumors with >5 EGFR gene copies per nucleus were interpreted as positive for gene amplification. Protein overexpression was scored according to standardized criteria originally developed for HER-2. EGFR mRNA levels, as measured by Affymetrix U133 Gene Chip microarray hybridization, were available in 63 of these tumors. HER-2 gene amplification by fluorescence in situ hybridization (FISH) and protein overexpression by immunohistochemistry were also studied. EGFR gene amplification (copy number range: 7-18; median: 12) was detected in 11/175 (6%) tumors, and protein overexpression was found in 13/175 (7%) tumors. Of the 11 tumors, 10 (91%) with gene amplification also showed EGFR protein overexpression (2+ or 3+ by immunohistochemistry). The EGFR mRNA level, based on Affymetrix U133 chip hybridization data, was increased relative to other breast cancer samples in three of the five tumors showing gene amplification. Exons 19 and 21 of EGFR, the sites of hotspot mutations in lung adenocarcinomas, were screened in the 11 EGFR-amplified tumors but no mutations were found. Three of these 11 tumors also showed HER-2 overexpression and gene amplification. Approximately 6% of breast carcinomas show EGFR amplification with EGFR protein overexpression and may be candidates for trials of EGFR-targeted antibodies or small inhibitory molecules.     

Myoglobinuria and transient acute renal failure in a patient revealing hypothyroidism

Muscle involvement in hypothyroidism commonly manifests as fatigue, myalgias, stiffness and slowed reflexes. We report a case of transient acute renal failure related to rhabdomyolysis and myoglobinuria in a 40 year old man that revealed the diagnosis of hypothyroidism with myopathy. The patient had proximal muscle weakness and tenderness, markedly raised muscle enzymes and deranged renal functions that normalised with thyroid replacement therapy. Hypothyroidism, though rare, should be considered a definite and authentic cause of rhabdomyolysis.     

Feasibility of using tissue microarrays for the assessment of HER-2 gene amplification by fluorescence in situ hybridization in breast carcinoma.

Tissue microarrays (TMAs) have been commonly used to study protein expression by immunohistochemistry (IHC). However, limited data exist on the validity of using TMAs to study gene amplification. In this study, we evaluated the feasibility of using breast carcinoma TMAs to study HER-2 gene amplification by fluorescence in situ hybridization (FISH). In addition, hormonal receptor status (ER and PR) and HER-2 protein overexpression by IHC were also studied, and results were compared with whole tissue sections. FISH for HER-2 was performed on formalin-fixed paraffin-embedded tissue from 114 invasive breast carcinomas both on whole tissue sections and on TMAs containing the same tumors. The TMA was created using 0.6-mm tissue cores with four sampled cores per tumor from the same tissue block used for whole section FISH. The PathVysion HER-2 probe kit was used for the FISH analysis. A ratio of HER-2:Chromosome17 > or =2.0 was interpreted as positive for gene amplification. The ER or PR was interpreted as positive when nuclear staining was detected in more than 10% of tumor cells. The HER-2 IHC (HercepTest; DAKO Corp, Carpinteria, CA) results were interpreted as 0, 1+, 2+, and 3+ according to standard criteria. The FISH results in the TMA and whole sections were concordant in 99 out of 101 successfully analyzed cases (99%). The FISH scores were consistent among the two to four cores in the majority of the cases. ER and PR results were concordant between whole sections and TMA cores in 97% (107/110) and 89% (97/109) cases, respectively. The overall concordance for HER-2 status by IHC between whole sections and TMA cores was 86% (94 out of 109 cases). TMAs are a reliable approach to study HER-2 gene amplification in a high throughput manner.     

Chromogenic in situ hybridization for the detection of HER-2/neu gene amplification in breast cancer with an emphasis on tumors with borderline and low-level amplification: does it measure up to fluorescence in situ hybridization?

We compared chromogenic in situ hybridization (CISH) with fluorescence in situ hybridization (FISH) for assessing HER-2/neu gene amplification using tissue microarrays (TMAs) made from formalin-fixed, paraffin-embedded tissue blocks from 113 cases of invasive breast carcinoma. TMAs were created using 0.6-mm tissue cores with 4 sampled cores per tumor. For both assays, a HER-2/chromosome 17 signal ratio of 2.0 or more was considered positive for gene amplification. The average ratio of cores from the same tumor was used for determination of gene amplification status of that particular tumor Of 113 cases, 102 were tested successfully by both assays. The results were concordant in 100.0% of cases (63 amplified; 39 nonamplified). All 22 cases of borderline (ratio, 2.0-2.5) or low-level (ratio, 2.6-3.9) amplification by FISH also showed HER-2 gene amplification by CISH. CISH is as sensitive as FISH in detecting borderline and low-level HER-2 amplification. Reliable recognition of the invasive carcinoma area by light microscopy and preservation of the test slides are added advantages of CISH. CISH performs as well as FISH in the analysis of HER-2 gene amplification in breast cancer and might have advantages in certain situations.     

An analysis of theα-adrenoceptor modulation of vasomotor tone at the level of lateral medullary pressor area (LMPA)

Summary Microinjection of noradrenaline and clonidine into lateral medullary pressor area (LMPA) of chloralose anaesthetized cats produced dose dependent decrease in blood pressure without affecting heart rate, while phenylephrine did not elicit any cardiovascular response. Selective ₂-adrenoceptor, antagonists idazoxan and piperoxan, microinjected locally, blocked the effects of the agonists but prazosin and phenoxybenzamine, which are relatively selective for ₁-adrenoceptors, failed to do so. Clonidine did not elicit any response in guanethidine pretreated cats but noradrenaline microinjected into LMPA of these animals induced a pressor response which was blocked by prazosin pretreatment. It is concluded that catecholaminergic fibres impinging upon this are inhibit the activity of the inhibitory second order baroreceptor neurone by activating ₁-adrenoceptors while ₂-adrenoceptors situated presynaptically on these inhibitory catecholaminergic nerve terminals are responsible for the manifestation of the hypotensive effect of clonidine and exogenously administered noradrenaline.     

Anhidrotic ectodermal dysplasia presenting as atrophic rhinitis and epistaxis—A case report and light microscopic study

An interesting case of anhidrotic ectodermal dysplasia which came with ozaena, epistaxis, headache and maggots is presented. Histopathology of nasal mucosa, scalp and forearm skin, and a pilocarpine sweat test helped to confirm the diagnosis. In the present state of our knowledge, this X-linked recessive condition has no cure but symptomatic treatment along with heat potection and protection of the eyes has a role to play in the management of these cases. It is hoped that a forgotten cause of atrophic rhinitis is resurrected.     

Hemostatic parameters in newborn--II. Sequential study during the first four weeks of life

A sequential study of kaolin cephalin clotting time (KCCT), prothrombin time (PT), thrombin time (TT), plasma fibrinogen and serum FDP was conducted during the first four weeks of life on term and preterm babies. A "physiological dip" of PT and TT was noted inappropriate for gestational age (AGA) babies both term and preterm; in case of KCCT, the dip was significant in term AGA babies only. At the end of four weeks, PT and TT had moderately improved in term babies but showed little improvement in preterm ones; KCCT reached almost an adult value in all babies except in preterm AGA and term LGA (large for gestational age) ones. Plasma fibrinogen showed no "physiological dip" and reached adult level in two to four weeks. Serum FDP levels were appreciably raised in preterm AGA babies only at birth and there too normalised by 72 h.     

Nucleus locus coeruleus: Evidence for α1-adrenoceptor mediated hypotension in the cat

Summary The Bezold-Jarisch reflex characterized by hypotension and bradycardia was elicited in anaesthetized artificially respired dogs (pretreated with a beta-adrenoceptor antagonist) using capsaicin 10 g/kg (i.v.). Intracisternal administration of the highly selective clonidine-like alpha₂ adrenoceptor agonists B-HT 920 (10 g/kg) or B-HT 933 (30 g/kg) significantly facilitated this reflex bradycardia. The involvement of central alpha₂-adrenoceptors is suggested as intracisternal administration of the alpha₂ adrenoceptor blocking drugs yohimbine (50 g/kg) and piperoxan (50 g/kg) antagonized this facilitation. B-HT 920 also facilitated the vagally mediated baroreceptor reflex to the hypertensive effect of intravenous noradrenaline (3 g/kg). Although the Bezold-Jarisch reflex and the baroreceptor reflex have different afferent pathways, both reflexes may either converge into a common pathway or have separate neuronal chains within the medulla; however, this study indicates that both have a similar central modulatory system stimulated by alpha₂ adrenoceptors.     

Perioperative outcomes of goal-directed versus conventional fluid therapy in radical cystectomy with enhanced recovery protocol

International Urology and Nephrology - The aim of this study is to evaluate the intra/perioperative fluid management and early postoperative outcomes of patients who underwent radical cystectomy...