PHEOCHROMOCYTOMA, THE GREAT MASQUERADER, PRESENTING AS REVERSIBLE CARDIOMYOPATHY: PRIMUM NON NOCERE.

Background: Pheochromocytoma, the great masquerader, can have a varied spectrum of clinical manifestations. It can often cause a diagnostic challenge despite the availability of modern investigation modalities. Case: We present the case of a 38-year-old male who presented with uncontrolled hypertension for the past 10 years and heart failure for one year. The diagnosis of pheochromocytoma was missed in the initial setting, leading to a biopsy of the retroperitoneal mass. Fortunately, the patient survived the procedure. Subsequently, with the involvement of a multi-disciplinary team, he was optimized for surgery under strict cardiac monitoring. After the complete excision of the tumour, he showed significant improvement not only in his clinical symptoms but also in his cardiac status. Conclusions: This case emphasizes the age-old medical phrase of 'Primum non nocere or first, do no harm'. Any invasive procedure in a pheochromocytoma can lead to a massive release of catecholamines causing a hypertensive crisis, pulmonary oedema, and even cardiac arrest. Any young patient presenting with hypertension or heart failure should be investigated for secondary causes. Cardiomyopathy due to pheochromocytoma is because of catecholamine overload and usually reverses or improves after curative surgery.

Biochemical analysis of ocular surface mucin abnormalities in dry eye: the canine model.

This study examines the canine model of keratoconjunctivitis sicca (KCS, 'dry eye') in order to establish the biochemical basis of altered ocular mucin secretion in this condition. It follows a previous examination of ocular mucins in the normal dog. Mucus was collected by suction from the ocular surface of dogs with KCS, and dispersed in guanidine hydrochloride containing a cocktail of protease inhibitors. Caesium chloride density gradient centrifugation was used to separate floating 'rafts' of cell membranes from gradients containing secreted mucins. Gradient fractions were collected into pools on the basis of differential staining by Periodic Acid Schiff, Wheat Germ Agglutinin, and antibodies to MUC5AC peptide. High molecular weight glycoproteins were purified from the pooled material by gel filtration chromatography. Membrane-associated glycoproteins were also derived from the membrane rafts using octyl glucoside extraction and/or reduction and alkylation. Secreted mucins and membrane extracts from KCS samples were compared to equivalent material obtained from normal eyes. Density gradient staining profiles for normal and KCS mucus were similar over the buoyant density range typical for secreted mucins, enabling the collection of identical pools of gradient fractions for direct comparison. The following differences were observed in KCS secreted mucins compared to normal samples: an increase in the proportion of mucin with low buoyant density; a decrease in mannose content detected with Concanavalin A lectin; an increase in N-acetylglucosamine structures detected with Lycopersicon esculentum lectin; increased migration and lack of evidence for distinct subunit structure on agarose gels. In membrane extracts, the main difference was the presence of T antigen (Gal beta 1-3GalNAc) in KCS. These results demonstrate alterations in the subunit linkage of mucins in KCS, and suggest that glycosylation, core protein expression and/or post-synthetic modification of ocular surface mucins may also be changed.

Demonstration of discrete secreted and membrane-bound ocular mucins in the dog.

Our aims were to separate and characterize secreted canine ocular mucins, and to provide definitive evidence of membrane-bound mucins at the canine ocular surface. Mucus was collected by suction from the ocular surface of normal dogs and dispersed in guanidine hydrochloride and a cocktail of protease inhibitors. Caesium chloride density gradient centrifugation separated secreted mucins from membranes, which were collected from the top of the gradients. Membranes were extracted with octyl glucoside and screened using lectins and anti-mucin antibodies. Gradient fractions containing secreted mucins were constituted into pools on the basis of differential lectin and antibody staining. High molecular weight material from each pool was purified by gel filtration. This material, and the membrane extract, were reduced and alkylated. Vacuum blotting of separated materials after agarose gel electrophoresis was used to compare subunit structure. Density gradient profiles indicated three principal secreted glycoprotein peaks: one staining strongly with anti-mucin antibodies. Gel filtration demonstrated that each contained high molecular weight material. Vacuum blots demonstrated the presence of two secreted glycoproteins with differently sized subunits. On the basis of buoyant density, one of these may be lipid complexed. Membrane extracted material stained with anti-mucin antibodies, and vacuum blotting of this material provided evidence for two membrane-bound components. In conclusion, we have shown that normal canine ocular mucus contains two secreted mucins, each exhibiting different subunit structure; one of these mucins may undergo lipid complexation. Normal canine ocular mucus also contains two membrane-bound mucins: one of which is unique among membrane mucins in showing subunit structure.

Androgen support of lacrimal gland function.

The effects of dihydrotestosterone (DHT) (1 mg/kg) on biochemical parameters related to lacrimal secretion, basal tear flow rate, and pilocarpine-stimulated lacrimal gland fluid secretion, in mature ovariectomized rabbits were studied. The effects of the synthetic estrogen diethylstilbestrol (DES) (100 micrograms/kg), on lacrimal gland biochemical parameters in normal mature female rabbits was also studied. Ovariectomy decreased the total serum levels of testosterone (T) by 88.5% and androstenedione by 35.9%, without changing the levels of dehydroepiandrosterone (DHEA) of its sulfate. Ovariectomy caused a significant regression of the lacrimal glands, decreasing total DNA by 35%, and total protein by 22%. DHT treatment of ovariectomized animals prevented lacrimal gland regression, increasing total gland DNA (31%) and total protein (18%). DHT treatment also increases Na+, K(+)-ATPase activity (29%) and beta-adrenergic receptor binding sites (23%) compared to the ovariectomized group. DHT increased pilocarpine stimulated lacrimal gland fluid secretion (13.26 +/- 1.47 microL/min) compared to the ovariectomized group (7.72 +/- 0.41 microL/min), but DHT treatment paradoxically decreased basal tear flow rate (1.02 +/- 0.04 microL/min) as compared to the ovariectomized rabbits (1.96 +/- 0.12 microL/min). DES decreased the total serum T from 59.33 +/- 10.54 pg/mL to 21.5 +/- 6.06 pg/mL. DES decreased total Na+,K(+)-ATPase by 12% and increased beta-adrenergic receptor binding sites by 83.3%. These results suggest that androgens play a major role in supporting lacrimal gland secretory function. Additionally, they suggest that estrogens may influence certain aspects of lacrimal functions, although it is not clear to what extent those actions are elicited directly or indirectly.

Ophthalmic cyclosporine in equine keratitis and keratouveitis: 11 cases.

Topical cyclosporine A was safely used in a series of 11 cases of equine keratitis and keratouveitis and appeared to be an effective anti-inflammatory agent in 9 cases. The clinical diagnoses included interstitial keratouveitis, endotheliitis, multifocal punctate keratopathy and a melting stromal ulcer. In most cases, the presence or absence of insidious bacterial infection was not conclusively determined. Topical cyclosporine A had no deleterious effects in this series of cases. The authors suggest that topical cyclosporine in both aqueous and lipid base vehicles should be investigated and evaluated as an alternative mode of achieving ocular immunosuppression.

Tear protein profiles vs. clinical characteristics of untreated and cyclosporine-treated canine KCS.

BACKGROUND: Topically administered cyclosporine A (CsA) decreases ocular surface inflammation in canine keratoconjunctivitis sicca (KCS) and exerts lacrimomimetic effects. This study was performed to find correlations between clinical signs and tear protein levels in untreated and CsA-treated canine KCS. METHODS: Clinical profiles were scored in 16 KCS-affected dogs before and 6 weeks after commencing treatment with 0.2% topical CsA emulsion. Tear samples were also collected using polished micropipettes for specific protein assay by high-performance liquid chromatography (HPLC) and enzyme-linked immunosorbent assay (ELISA). RESULTS: Tear levels of serum proteins correlated with conjunctival clinical signs. Levels of lacrimal gland proteins in tears correlated most often with corneal clinical signs. CONCLUSIONS: The inflammatory features of KCS appear to link conjunctival signs to serum proteins in tears, while corneal signs are linked to lacrimal gland proteins.

Microorganisms isolated from the corneal surface before and during topical cyclosporine treatment in dogs with keratoconjunctivitis sicca.

The effect that topical administration of cyclosporine would have on the number and type of microorganisms isolated from the corneal surface of dogs with keratoconjunctivitis sicca was studied. Schirmer tear test wear performed on and corneal swab specimens were collected from 61 eyes of 31 dogs with keratoconjunctivitis sicca prior to and after 3, 6, and 12 months of treatment with cyclosporine. In eyes that responded to cyclosporine treatment (Schirmer tear test value increased by > or = 5 mm/min, compared with pretreatment value), the percentage of eyes from which bacteria were isolated 3, 6, and 12 months of treatment was significantly (P < 0.001) less than the percentage from which bacteria were isolated prior to treatment. However, among eyes that did not respond to treatment, we did not detect a significant change over time in prevalence of bacteria or type of bacteria isolated. The percentage of eyes from which fungi were isolated decreased during treatment; however, the small number of eyes in which fungal culture results were initially positive precluded demonstration of a significant differences over time in the frequency with which specific bacterial genera were isolated, with the exception of beta-hemolytic Streptococcus spp. Opportunistic corneal infections were not detected even though none of the dogs received antibiotics. An increase in production of tears, which contain anti-infection, proteins, was believed to be the primary factor responsible for the decrease in the percentage of eyes from which microorganisms could be isolated.

Modification of the orbital rim anchorage method for surgical replacement of the gland of the third eyelid in dogs.

Excision of a prolapsed gland of the third eyelid predisposes a dog to develop keratoconjunctivitis sicca later in its lifetime, and replacement, rather than excision, of the gland is the preferred method of treatment. One method of gland replacement involves suturing the prolapsed gland to the periosteum of the ventral orbital rim. As originally described, however, the procedure required that the surgeon make a U-turn with the needle and suture within the confines of the ventral fornix. This report describes modifications to the original technique that eliminate this difficult step and make it easier for the surgeon to obtain a secure bite of the orbital periosteum.

Influence of vehicle and anterior chamber protein concentration on cyclosporine penetration through the isolated rabbit cornea.

The transcorneal penetration of cyclosporine A has been determined from each of three vehicles across isolated cornea into simulated aqueous humor containing either 50 mg % protein (0.5 mg/ml; as found in a normal eye) or 5000 mg % protein (50 mg/ml; as found in an inflamed eye). Cyclosporine entered the corneal epithelium and stroma/endothelium as well as passed through the cornea from an alpha cyclodextrin vehicle. Entry into the epithelium and stroma/endothelium occurred from an ointment vehicle with limited detectable anterior chamber penetration using 50 mg % protein solution in the anterior chamber. From corn oil vehicle, cyclosporine penetrated across the cornea with a permeability equal to that of alpha cyclodextrin vehicle. The concentration of cyclosporine in both corn oil and ointment vehicles is 8 times greater than that in alpha cyclodextrin vehicle resulting in a flux from corn oil vehicle about 7 or 8 times greater than that seen after alpha cyclodextrin vehicle. The amounts retained in the cornea, however, were relatively low after corn oil compared to cyclodextrin. The penetration of cyclosporine from either the cyclodextrin vehicle or ointment was at least doubled in the presence of 5000 mg % protein in the simulated aqueous humor relative to that seen in 50 mg % protein. This data indicates that the (presumed) absorption and binding of drug by the excess protein in the simulated aqueous humor may have removed free cyclosporine from the solution and sustained a high concentration gradient of free solute across the cornea.(ABSTRACT TRUNCATED AT 250 WORDS)

Prolactin localization, binding, and effects on peroxidase release in rat exorbital lacrimal gland.

Prolactin immunoreactivity has been detected in human tears and in lacrimal glands, and it has been suggested that this hormone might be a modulator of lacrimal secretion as well as a component of lacrimal gland fluid. The present study was designed to confirm the immunocytochemical localization of prolactin in the rat lacrimal gland, to determine the source of the prolactin, and to evaluate the acute effects of prolactin on lacrimal secretory function. We have confirmed that prolactin-like immunoreactivity is present in secretory vesicles of acinar cells of male and female Sprague-Dawley rats. Prolactin message was present at detectable levels in RNA extracts of lacrimal glands from males, indicating that at least a component of the prolactin-like immunoreactivity was the product of synthesis within the lacrimal glands. Crude membrane fractions from acini isolated from males bound 43.1 +/- 3.2 femtomoles prolactin/mg protein (mean +/- standard error of the mean; n = 6), which was significantly (P less than 0.01) more than comparable fractions from females (15.4 +/- 2.4 fmoles/mg protein, n = 6). Preincubating membranes at 65 degrees for 20 min to release endogenous ligands increased prolactin binding to 84.8 +/- 20.8 fmoles/mg protein for males and 63.8 +/- 17.4 fmoles/mg protein for females (P greater than 0.1), suggesting that, on average, similar numbers of receptors are expressed in acinar cells of male and female rats but a larger fraction of the receptors is occupied by endogenous prolactin-like peptides in females. Because prolactin binding triggers prolactin receptor internalization in various cell types, we propose that the prolactin-like immunoreactivity in lacrimal acinar cells of females has been accumulated from the circulation, while the immunoreactivity seen in males results, at least in part, from de novo synthesis. Ovine prolactin at concentrations of 10-20 ng/ml inhibited carbachol-induced peroxidase release by 19.6% +/- 6.9% (n = 8, P less than 0.02) but failed to alter peroxidase release in the absence of carbachol. These observations suggest that prolactin might function as an endocrine, paracrine, or autocrine modulator in the lacrimal gland.