Specific impairment of endothelium-dependent vasodilation in subjects with type 2 diabetes independent of obesity

In subjects with type 2 diabetes in whom an impaired response to an endothelial-dependent vasodilator has been characterized, the populations have also been at least moderately obese. Obesity has been characterized as an independent predictor of endothelial dysfunction in nondiabetic subjects. We hypothesized that in normotensive subjects with type 2 diabetes compared with age-matched control subjects, 1) endothelium-dependent vasodilation, as demonstrated by the forearm blood flow (FABF) response to intraarterial acetylcholine, would be decreased; 2) endothelium-independent vasodilation, as demonstrated by the FABF response to intraarterial nitroprusside, would be similar; 3) the degree of insulin resistance, as measured by the insulin sensitivity index (SI), would predict greater impairment in the FABF response to acetylcholine; and 4) these relationships would be independent of obesity. We measured FABF by venous occlusion plethysmography during brachial arterial infusions of the endothelium-dependent vasodilator acetylcholine and the endothelium-independent vasodilator nitroprusside in 20 control and 17 subjects with type 2 diabetes. We measured SI using the frequently sampled i.v. glucose tolerance test. Among the diabetic relative to the control subjects we identified a decrease in the acetylcholine-mediated percent increase in FABF (P = 0.02). Using the absolute FABF response to acetylcholine and including adjustments for body mass index and other covariates, the overall group difference remained and was noted to be greatest in those subjects who had lower baseline FABFs. In contrast, no significant difference in the nitroprusside-mediated increase in the percent change FABF was identified between groups (P = 0.30). Finally, the degree of insulin resistance, as measured by SI, did not independently predict greater impairment of the FABF response to acetylcholine. This study is the first to identify specific endothelial cell dysfunction that remains significant after adjustment for obesity in a population of normotensive subjects with type 2 diabetes.     

Increased LTB4 metabolites and PGD2 in BAL fluid after methacholine challenge in asthmatic subjects

The bronchoconstrictor potency of inhaled methacholine is widely used to assess airway responsiveness. However, evidence has accumulated that methacholine inhalation challenge may lead to an inflammatory response in the lower respiratory tract. We therefore compared cellular, leukotriene and prostanoid profiles in bronchoalveolar lavages (BAL) obtained five hours after methacholine challenge to control lavages without prior challenge. Eight subjects with asymptomatic to mild bronchial asthma and nine nonatopic healthy controls were enrolled in the study. Without prior challenge, the percentage of BAL eosinophils was higher in the asthmatic subjects ((mean +/- SD), 1.1 +/- 0.9%) than in the control subjects (0.1 +/- 0.1%. Leukotriene B4 (LTB4), and its omega-oxidation products (20-OH-LTB4 and 20-COOH-LTB4) were the only leukotrienes detectable in the baseline BAL fluids in five of the eight asthmatic patients. After methacholine challenge, no change in BAL cell profile occurred, but in the asthmatic patients, the total amounts of LTB4 and its omega-oxidation products rose from 0.52 +/- 0.50 ng.ml-1 (pre-challenge) to 1.55 +/- 1.32 ng.ml-1 (post-challenge), and prostaglandin D2 (PGD2) rose from 49.1 +/- 15.7 (pre-challenge) to 94.4 +/- 25.4 pg.ml-1 (post-challenge), with no change in 6-keto-PGF1 alpha, thromboxane B2 (TXB2), and prostaglandins F2 alpha and E2 (PGF2 alpha and PGE2). In the healthy controls, no consistent change in BAL cell profile and mediators occurred after methacholine provocation. We conclude that inhaled methacholine stimulates LTB4 and PGD2 release in asthmatics, but not in healthy controls, without affecting the number of inflammatory cells in BAL fluid.     

Indications for conjunctival transplantation

Long-term follow-up (two to five years) of 12 unilateral chemical burn patients treated by conjunctival transplantation shows permanent stabilization of the ocular surface. The procedure was used in another group of five patients with unilateral recalcitrant epithelial defects. Regardless of the etiology of the epithelial defect, prompt healing of the surface occurs after conjunctival transplantation with no further stromal loss and long-term stabilization of the surface. Such results suggest that epithelial replacement may be a valuable therapeutic approach to a variety of ocular surface disorders.     

Results of treatment in malignant epithelial conjunctival tumors

Existing catheter implantation techniques violate a fundamental premise of wound healing. The immediate presence of the catheter in the post operative surgical wound forms a passage for permanent colonization of the catheter tunnel and cuff(s). This is manifested by the almost universal presence of the biologic products of bacterial growth (biofilm) on the external and internal surfaces of these catheters. The Moncrief-Popovich catheter and implantation technique are designed to address this problem. The Moncrief-Popovich catheter is implanted in the standard fashion, except that the external segment of the catheter is buried subcutaneously at the time of implantation. After allowing 3-5 weeks for tissue in-growth in a sterile environment, a small incision is made in the skin through which the external segment of the catheter is exteriorized and attached to an adapter. A 2 year trial was conducted in 59 patients, comprising 530 patient-months of experience; the incidence of peritonitis was one episode for every 29.4 patient months. All but three of the patients used the standard spike exchange technique. In a recently initiated study using disconnect procedures in 63 of the 74 patients studied, the peritonitis rate was one episode for every 28.7 patient-months; patient-months have totalled 201.2 to date. There was a rate of one exit site infection every 12.57 patients-months. It was concluded that the Moncrief-Popovich catheter and implantation technique result in a substantial decrease in the incidence of peritonitis for patients using the standard spike exchange system.     

Nucleolar organizer regions in conjunctival nevi and melanomata

The objective of this study was to compare the argyrophil nucleolar organizer region (Ag-NOR) counts of conjunctival nevi and melanomata and to compare the efficacy of this method in their differential diagnosis. Nine histologically diagnosed conjunctival nevi and three conjunctival malignant melanomas were studied. Representative sections were stained using the AgNOR technique. Fifty cells of each melanocytic lesion were randomly selected without knowing their histologic diagnosis. The AgNORs were visualized at a magnification of x1000. They consisted of clusters >1 micron in diameter and of satellites <1 micron in diameter, which were counted and recorded for each cell separately. The mean AgNOR count for the nevi was 1.12 clusters and 1.72 satellites per cell, while the count for the melanomas was 1.6 clusters and 6.8 satellites per cell. These results are statistically significant. There was no overlap between the number of AgNOR clusters and satellites in conjunctival nevi and melanomas, indicating that the AgNOR count might be a useful tool in distinguishing benign from malignant conjunctival melanocytic lesions.     

Combined analysis of two studies using the conjunctival allergen challenge model to evaluate olopatadine hydrochloride, a new ophthalmic antiallergic agent with dual activity

PURPOSE: To evaluate the effectiveness and safety of olopatadine hydrochloride and to determine its optimal concentration and the onset and duration of action for treating allergic conjunctivitis. Olopatadine is a new topical ophthalmic antiallergic agent that demonstrates activity as both an antihistamine and a mast cell stabilizer. Two double-masked, randomized, placebo-controlled, contralateral eye comparison studies were conducted using the conjunctival allergen challenge model. METHODS: A total of 169 subjects received 0.05% or 0.1% olopatadine. Study subjects were healthy adult men and women with a history of active allergic conjunctivitis within the previous two seasons but not receiving current treatment. With an allergen dose that produced signs and symptoms of allergic conjunctivitis at visits 1 and 2, the conjunctival allergen challenge was performed 27 minutes after study drug administration at the third visit (onset-of-action challenge) and at 8 hours after study drug administration at the fourth visit (duration-of-action challenge). Olopatadine was administered in one eye and placebo in the opposite eye. Itching and redness were scored for both eyes at 3, 10, and 20 minutes after the conjunctival allergen challenge. RESULTS: Both 0.05% and 0.1% concentrations of olopatadine were significantly (P < .05) more effective than placebo in inhibiting itching and redness at all evaluations when administered 27 minutes or 8 hours before the conjunctival allergen challenge. There were no serious or drug-related ocular or nonocular adverse events in either study. CONCLUSION: These findings demonstrate the rapid and prolonged (at least 8 hours) ocular antiallergic action of olopatadine.     

Acute monoblastic leukaemia with conjunctival tumours

We describe an unusual occurrence of bilateral conjunctival tumours in a 25-year-old woman. This was the first sign of relapse of acute monoblastic leukaemia. There was also both marrow relapse and subsequent skin infiltration. No central nervous system involvement was detected. The tumours appeared as pink raised lesions in the upper conjunctivae of both eyes. They were not associated with pain or visual impairment. Conjunctival tumour biopsy revealed a dense mononuclear cell infiltration. Complete remission (conjunctival tumours, skin infiltration and bone marrow) was attained following systemic chemotherapy in combination with intrathecal chemotherapy.     

New model of conjunctival scarring in the mouse eye

AIMS: To establish a simple model of conjunctival wound healing in the mouse eye. METHODS: 4 week old BABL/c mouse eyes were studied over a 14 day period. Surgical procedure under general anaesthesia involved a blunt dissection of the conjunctiva performed by injection of 25 microliters of PBS via a 27 gauge needle into one eye, while the contralateral eye was used as control. Mice were assessed clinically and sacrificed at 1, 2, 3, 7, and 14 days after surgery. Enucleated eyes were prepared for histological analysis. Development of scar tissue was studied with haematoxylin and eosin, oxidation aldehyde fuchsin, and van Gieson stains, with assessment of cellularity, extracellular matrix formation, and wound characterisation. RESULTS: Histological analysis revealed a marked and characteristic healing response initiated by a predominantly granulocytic inflammatory reaction at day 1 with peak fibroblast activity 3 days after surgery. Oxytalan fibres and newly laid collagen fibres were detected early in the subconjunctival wound area and up to 7 days after surgery. Remodelling and complete organisation of scar tissue was evident by day 14. CONCLUSION: A single subconjunctival injection in the mouse eye results in a marked and consistent healing response. This represents a simple, inexpensive, and reliable animal model of conjunctival scarring. The mouse is a biologically well characterised animal model and allows the use of a wide variety of molecular tools. There are potentially significant clinical applications, in particular in investigating the effects of modulating agents such as antimetabolites, growth factors, and their antagonists on conjunctival scarring.     

Circulating basophils in normal subjects and in subjects with hay fever

The relationship of hay fever symptoms and changes in the number of circulating basophils was studied in 12 subjects clinically sensitive only to ragweed and in 10 nonatopic subjects before, during, and after the ragweed season. Total white blood counts, absolute basophil counts, and symptom scores were recorded twice weekly from mid-June through October, 1974, and compared with the ragweed pollen count. The results indicated that the absolute and relative number of basophils were significantly elevated (p less than 0.001) in the hay fever group when symptoms occurred. As the symptom score of the allergic group increased during the ragweed season, the number of basophils also increased, only to decrease to control values when symptoms subsided. The basophil counts of the atopic group were significantly higher than those of the nonatopic group during the control periods. The nonatopic group also showed a significant elevation of basophils during the ragweed season, but to a much lesser extent than the atopic group. It is concluded that: (1) subjects with symptomatic hay fever have a significantly elevated absolute and relative basophil count which correlates with the exacerbation and remission of symptoms; (2) nonatopic subjects also have a small but significant elevation of basophils during the ragweed season; and (3) the elevation of basophils in the atopic group during symptoms is significantly greater than in the nonatopic group during the ragweed season.     

Reconstruction of filtering blebs with free conjunctival autografts

BACKGROUND: Situations arise in which the surgical repair or revision of filtering blebs is either technically impossible or inadequate, and total reconstruction becomes necessary. This is most frequently encountered in eyes that have undergone multiple procedures, resulting in significant bulbar conjunctival scarring and episcleral fibrosis. METHODS: To preserve the pre-existing filtration site, the authors successfully treated five such patients in whom conjunctival scarring adjacent to and surrounding the blebs precluded local revision, by transplanting free conjunctival autografts. Two patients required grafting from the fellow eye. Specific modifications from previously reported conjunctival flap techniques were used to enhance graft healing and continued filtration. RESULTS: Satisfactory intraocular pressure control was maintained in all patients receiving minimal to no anti-glaucomatous medications with an average follow-up of 42.6 months (range, 7-90 months). No patient had a significant decrease in visual acuity or surgical complications. CONCLUSION: Free conjunctival autografting techniques are a useful adjunct in the surgical revision of leaking, failed, or migrating filtration blebs.