The association between carotid disease, arterial stiffness and diabetic retinopathy in type 2 diabetes: the Fremantle Diabetes Study Phase II.

AIM: To determine whether macrovascular disease assessed by carotid ultrasonography and arterial stiffness by pulse wave velocity are independently associated with diabetic retinopathy in type 2 diabetes. METHODS: A random subgroup of surviving participants with type 2 diabetes from the Fremantle Diabetes Study Phase II were invited to take part in this sub-study in 2018-2019. In addition to standardized questionnaires, a physical examination and fasting biochemical tests, each underwent dilated colour fundus photography, carotid arterial ultrasonography with measurement of the intima-media thickness (IMT) and quantification of the degree of stenosis, and pulse wave analysis calculation of the carotid-femoral pulse wave velocity (cfPWV). The cross-sectional association between arterial disease parameters and diabetic retinopathy was assessed using generalized estimating equation models which enabled both eyes to be included in the analysis. RESULTS: Some 270 participants [mean ± sd age 72 ± 9 years, 153 (57%) men and median (IQR) diabetes duration 15 (11-22) years] were included in analysis. Of 524 assessable eyes, 82 (16%) had diabetic retinopathy. In multivariable analysis, significant independent associates of diabetic retinopathy were age at diabetes diagnosis (inversely), HbA1c , insulin treatment and urinary albumin to creatinine ratio (all P ≤ 0.022), as well as cfPWV [odds ratio (OR) 1.13, 95% confidence interval (CI) 1.03, 1.23 per 1 m/s increase; P = 0.008] and common carotid artery (CCA) IMT ≥1 mm (OR 2.95, 95% CI 1.21, 7.23; P = 0.018). CONCLUSIONS: The association between diabetic retinopathy and CCA IMT suggests that carotid disease may share cardiovascular risk factors with diabetic retinopathy. The association between diabetic retinopathy and cfPWV may reflect the consequences of altered intravascular haemodynamics.

De Novo Donor-Specific HLA Antibodies Are Associated With Rapid Loss of Graft Function Following Islet Transplantation in Type 1 Diabetes.

Outcomes after islet transplantation continue to improve but etiology of graft failure remains unclear. De novo donor-specific human leukocyte antigen (HLA) antibodies (DSA) posttransplant are increasingly recognized as a negative prognostic marker. Specific temporal associations between DSA and graft function remain undefined particularly in programs undertaking multiple sequential transplants. Impact of de novo DSA on graft function over 12 months following first islet transplant was determined prospectively in consecutive recipients taking tacrolimus/mycophenolate immunosuppression at a single center. Mixed-meal tolerance test was undertaken in parallel with HLA antibody assessment pretransplant and 1-3 months posttransplant. Sixteen participants received a total of 26 islet transplants. Five (19%) grafts were associated with de novo DSA. Five (31%) recipients were affected: three post-first transplant; two post-second transplant. DSA developed within 4 weeks of all sensitizing grafts and were associated with decreased stimulated C-peptide (median [interquartile range]) at 3 months posttransplant (DSA negative: 613(300-1090); DSA positive 106(34-235) pmol/L [p = 0.004]). De novo DSA directed against most recent islet transplant were absolutely associated with loss of graft function despite maintained immunosuppression at 12 months in the absence of a rescue nonsensitizing transplant. Alemtuzumab induction immunosuppression was associated with reduced incidence of de novo DSA formation (p = 0.03).

Attainment of metabolic goals in the integrated UK islet transplant program with locally isolated and transported preparations.

The objective was to determine whether metabolic goals have been achieved with locally isolated and transported preparations over the first 3 years of the UK's nationally funded integrated islet transplant program. Twenty islet recipients with C-peptide negative type 1 diabetes and recurrent severe hypoglycemia consented to the study, including standardized meal tolerance tests. Participants received a total of 35 infusions (seven recipients: single graft; 11 recipients: two grafts: two recipients: three grafts). Graft function was maintained in 80% at [median (interquartile range)] 24 (13.5-36) months postfirst transplant. Severe hypoglycemia was reduced from 20 (7-50) episodes/patient-year pretransplant to 0.3 (0-1.6) episodes/patient-year posttransplant (p < 0.001). Resolution of impaired hypoglycemia awareness was confirmed [pretransplant: Gold score 6 (5-7); 24 (13.5-36) months: 3 (1.5-4.5); p < 0.03]. Target HbA1c of <7.0% was attained/maintained in 70% of recipients [pretransplant: 8.0 (7.0-9.6)%; 24 (13.5-36) months: 6.2 (5.7-8.4)%; p < 0.001], with 60% reduction in insulin dose [pretransplant: 0.51 (0.41-0.62) units/kg; 24 (13.5-36) months: 0.20 (0-0.37) units/kg; p < 0.001]. Metabolic outcomes were comparable 12 months posttransplant in those receiving transported versus only locally isolated islets [12 month stimulated C-peptide: transported 788 (114-1764) pmol/L (n = 9); locally isolated 407 (126-830) pmol/L (n = 11); p = 0.32]. Metabolic goals have been attained within the equitably available, fully integrated UK islet transplant program with both transported and locally isolated preparations.

The psychiatric uses of cold wet sheet packs.

The cold wet sheet pack is a treatment that is seldom discussed anymore. The authors present results of a national survey which demonstrated that this treatment is rarely used in modern American psychiatry. They retrospectively review its recent use for 46 hospitalized psychiatric patients and conclude that the treatment is safe and has interesting and useful effects that go beyond the concept of simple restraint. Further study of treatment with cold wet sheet packs is recommended before it disappears altogether.

Predicting deterioration in previously healthy infants hospitalized with respiratory syncytial virus infection.

OBJECTIVE: To estimate the incidence of clinical deterioration leading to intensive care unit transfer in previously healthy infants with respiratory syncytial virus (RSV) infection hospitalized on a general pediatric unit and, to assess the hypothesis that history, physical examination, oximetry, and chest radiographic findings at time of presentation can accurately identify these infants. STUDY DESIGN: A virology database was used to identify and determine the disposition of all children 80 and an O(2) saturation <85% at time of presentation each had a specificity >97% for predicting subsequent deterioration. Each parameter, however, had a sensitivity

Increase in admission threshold explains stable asthma hospitalization rates.

BACKGROUND: Asthma morbidity and mortality has increased substantially in recent years, but asthma hospitalization rates among many geographic and sociodemographic groups have remained stable. Observations on asthma hospitalization rates and severity of acute episodes might provide valuable insight into the functioning of the health care system during this period of health care reform. OBJECTIVE: To analyze changes between 1991 and 1995 in childhood asthma hospitalization rates and severity of acute episodes. DESIGN AND METHODS: All 29 329 hospitalizations, including 2028 for asthma, for the 198 893 children (<19 years of age) in Monroe County (Rochester), New York, were studied during this 5-year period. Severity was determined by hospital record review on a 22% random sample. Using the worst oxygen saturation (SaO(2)) during the first 24 hours of hospitalization as the primary index of severity, episodes were categorized as mild (0 to >/=95), moderate (90 to 94), or severe (<90). RESULTS: Hospitalization rates are expressed as hospitalizations per 1000 child-years. The overall asthma hospitalization rate was 2.04 (95% confidence interval, 1.95-2.13). The overall annual asthma hospitalization rate remained relatively stable from 1991 (1.90) to 1995 (2.31), whereas the hospitalization rates for severe asthma rose 270%-from 0.57 to 1.55-during this period. Simultaneously, the hospitalization rates for mild asthma decreased from 0.26 to 0.12. As a proportion of all asthma hospitalizations between 1991 and 1995, severe episodes increased from 31.5% to 60.4%; conversely, mild episodes decreased from 14.1% to 4.7%. CONCLUSIONS: Severity increased significantly among children hospitalized for asthma while the overall asthma hospitalization rate remained stable. It seems that the health care system in this community has responded to an increase in severity of asthma by raising the severity threshold for admission.

Platelets, coagulation and fibrinolysis in patients with diabetic retinopathy.

Twenty control subjects, 12 insulin treated and 10 non-insulin treated diabetics were studied. All diabetics had retinopathy documented by fluorescein angiography and fluorophotometry. Factor VIIIR:Ag and plasma fibrinogen concentrations were elevated in both diabetic groups, but more so in the insulin treated patients. Within this latter group the plasma fibrinogen was also correlated with the degree of retinopathy. Platelets separated on linear isosmolar Percoll gradients showed an increase in intraplatelet beta TG content and concentration and a slight increase in volume of the lightest platelets in the insulin treated diabetics. Plasma platelet factor 4 and antithrombin III concentrations were normal and plasma beta TG levels were elevated only in those patients with renal insufficiency. Platelet aggregometry was performed in 18 diabetic subjects and found to be normal. It is concluded that abnormalities of coagulation and platelets in diabetes are determined by metabolic factors rather than the severity of microvascular disease per se.

Specular microscopy in the identification of deep corneal opacities.

Specular microscopy provides a level of magnification and differentiation of detail which approaches that of a histological examination, and has the advantage of being a noninvasive procedure. This makes specular microscopy useful not only in examining the corneal endothelium, but also in identifying deep corneal opacities, which fall into two broad groups: 1) exogenous materials deposited in the cornea; and 2) endogenous pathologic corneal changes. Exogenous materials in the cornea have a wide variety of appearances, including the typical appearance of caterpillar hairs, the multifaceted appearance of glass foreign bodies, the regular geometric appearance of cholesterol crystals and cigar-shaped myeloma crystals or the more irregular deposits of chlorpromazine. Endogenous changes include ghost vessels, larger striate corneal nerves, fasciculi of fine parallel lines in keratoconus, criss-cross irregularly running lines in resolved keratitis, and a shagreen or cellophane-like appearance suggesting thickening of Descemet's membrane. While some deep corneal opacities are easily diagnosed clinically, the nature of others may be difficult to determine and specular microscopy is a valuable aid in such cases.

Impact of low birth weight on early childhood asthma in the United States.

OBJECTIVE: To estimate the independent contribution of birth weight to asthma prevalence among children younger than 4 years in the United States and to compare the magnitude of its effect on asthma between African American and white children. DESIGN: Cross-sectional analysis using the 1988 National Maternal-Infant Health Survey and 1991 Longitudinal Follow-up Survey. SETTING: United States. PATIENTS: Eight thousand seventy-one subjects, selected from a randomized, systematic population-based sample and weighted to be nationally representative, who completed both initial and longitudinal follow-up surveys and reported information on asthma diagnosis. MAIN OUTCOME MEASURES: Birth weight and other sociodemographic factors linked to birth outcome were analyzed for independent association with physician-diagnosed asthma by age 3 years. RESULTS: The prevalence of asthma varied by birth weight category: 6.7% in children 2500 g or more at birth, 10.9% in children 1500 to 2499 g at birth, and 21.9% in children less than 1500 g at birth (very low birth weight [VLBW]) (P<.001). Some of the characteristics shown to be independently associated with asthma included: VLBW (odds ratio [OR], 2.9; 95% confidence interval [CI], 2.3-3.6), moderately low birth weight (OR, 1.4; 95% CI, 1.1-1.8), and African American race (OR, 1.9; 95% CI, 1.6-2.4). In stratified analyses, the independent association between VLBW and asthma in white and African American populations was: OR(white), 3.1 (95% CI, 2.2-4.3) and OR(African American), 2.5 (95% CI, 2.0-3.3). The prevalence of VLBW, however, was tripled in African American compared with white children (1.8% vs 0.6%). CONCLUSIONS: These data confirm findings of other studies that identify a strong independent association between low birth weight and asthma. For this 1988 national birth cohort, an estimated 4000 excess asthma cases were attributable to birth weight less than 2500 g. Although the strength of the independent association between VLBW and asthma was smaller in the African American population, the substantially increased prevalence of VLBW in this community may contribute to the disproportionately increased prevalence of asthma among African American children.

How commonly are children hospitalized for asthma eligible for care in alternative settings?

OBJECTIVE: To estimate the proportion of children hospitalized for acute asthma exacerbation who might be cared for successfully in alternative settings such as short-stay units or in-home nursing. DESIGN: Descriptive study based on analysis of hospital discharge files and on retrospective medical record review of a random sample of asthma hospitalizations. METHODS: The 2028 asthma hospitalizations between 1991 and 1995 for children (aged <19 years) dwelling in Rochester, NY, were studied. Measures included the duration of frequent administration of nebulized medication (2 or more times in a 4-hour period), worst oxygen saturation levels, deterioration, and hospital length of stay. Oxygen saturation values and nebulized medication frequency were determined by hospital record review on a random sample of 443 asthma episodes. Length of stay was available for all admissions. RESULTS: Worst oxygen saturation following hospital admission was 95% or greater, 90% to 94%, and less than 90% for 21.3%, 51.6%, and 27.1% of episodes, respectively. Children received frequent nebulized medication treatments for a mean of 2.0 nursing shifts (8 hours per shift), although they remained hospitalized, on average, for 4.3 nursing shifts longer. Deterioration to a critical level of severity was uncommon. Among children initially admitted to the regular pediatric inpatient unit, only 0.7% subsequently deteriorated to the point that they were transferred to the critical care unit. CONCLUSION: More than 70% of asthma hospitalizations in this community could be cared for in alternative settings with supplemental oxygen, nebulized medication treatments, and close nursing observation provided, in most cases, for 2 nursing shifts.

Excimer laser filtration surgery.

PURPOSE: In order to remove precisely scleral tissue overlying Schlemm's canal with minimal trauma as an outpatient procedure under local anesthetic, we used a VisX Twenty/Twenty excimer laser. METHODS: We performed excimer laser filtration in three enucleated pig eyes, seven enucleated human eyes, and seven eyes of seven patients with severe glaucoma. Precise ablation to Schlemm's canal was confirmed by scanning electron microscopy in the enucleated eyes. For the patients, a local anesthetic was used, and a custom-made holder was used to mobilize the conjunctiva and fix the eye. RESULTS: A functional sclerostomy was obtained with 1,780 to 5,965 pulses, using a 2 x 1-mm slit. In our mean follow-up of nine months (range, six to 12 months) the excimer laser filtration technique achieved controlled filtration in five of seven patients and minimized conjunctival trauma. One patient subsequently underwent cataract extraction. CONCLUSIONS: This study indicates that excimer laser filtration is an effective technique for achieving filtration in glaucoma. It may reduce the complications of glaucoma filtration surgery, particularly the incidence of shallow anterior chamber postoperatively, as it leaves the trabecular meshwork intact.

Blood groups as genetic markers in glaucoma.

A series of 474 mixed cases of glaucoma was assessed to determine whether there were any genetic differences between different types of glaucoma. A careful distinction was made between chronic open angle glaucoma (COAG), acute and chronic angle closure glaucoma, ocular hypertension, low tension glaucoma, patients with large cup disc ratios, and various types of secondary glaucoma including pseudoexfoliation of the lens capsule, uveitic and traumatic glaucoma. Using ABO blood groups, Rhesus groups, ABH secretion or non-secretion, and phenylthiourea tasting we identified certain differences. The differences from normal were significant decrease in Rh-negative patients in chronic closed angle glaucoma (p less than 0.05), a decrease in ABH secretors in ocular hypertension (p less than 0.01), and fewer HB secretors in patients with COAG (p less than 0.02). There was a significant decrease in AH secretors and increase in HB secretors in both pseudoexfoliation with raised intraocular pressure compared with COAG (p less than 0.01) and in secondary glaucomas as a group compared with COAG (p less than 0.01). Tasters of phenylthiourea were more common in traumatic and uveitic glaucoma than in normal controls (p less than 0.05). These results suggest that secondary glaucoma develops in different subjects from COAG, while patients who develop a rise in intraocular pressure proceed to cupping and field loss if they have a certain genetic constitution. The groups of patients are too small for the differences to be of great prognostic value.

Haemolytic glaucoma occurring in phakic eyes.

The occurrence of haemolytic glaucoma in phakic eyes due to ghost cells has not previously been reported. Three cases of haemolytic glaucoma occurring over two years after massive vitreous haemorrhage in patients with an intact lens iris diaphragm are described. In one case there was histological confirmation of the presence of ghost cells in the anterior chamber. The mechanism proposed for the passage of ghost cells to the anterior chamber is through a defect in the anterior hyaloid face, created as the vitreous liquefies and degenerates. The reported cases were satisfactorily treated by trabeculectomy with anterior chamber washout, which management has not previously been reported in haemolytic glaucoma.

Iris atrophy with hypoperfusion and microneovascularisation.

A series of 17 patients with stromal atrophy, hypoperfusion, and microneovascularisation of the iris investigated in the Glaucoma Investigation and Research Unit are described, and their iris angiograms were compared with those of normal irides of patients in the same age group seen in general clinics. In all but one of the 17 cases this iris atrophy was associated with glaucoma or ocular hypertension, which appeared to be secondary to the iris changes. The condition was bilateral and presented a typical slit-lamp appearance, with subtle evidence of microneovascularisation. There was neither history nor clinical evidence of previous trauma, heterochromia, or intraocular inflammation. The commonest form of iris atrophy affected the inner third of the iris stroma in a patchy manner, often with sparing above. However, diffuse atrophy occurred in two cases, and there were two cases of 'senile tears' of the iris. Some accompanying atrophy of the pigment epithelium was usual but less prominent. The changes on fluorescein angiography of the iris included the late appearance of dye with a long arteriovenous circulation time, fewer arteries than normal with sectorial hypoperfusion, leakage of dye from the pupil margin and peripupillary neovascularisation, stromal tufts, and sometimes more complex stromal microneovascularisation. An expanded prominent lesser vascular circle was a common feature of the condition. The condition is bilateral and distinct from other forms of iris atrophy. In all cases the iris changes appeared to be secondary to the vascular hypoperfusion and were not consistently associated with evidence of gross vascular disease. All patients had grey (blue) irides, and this may be an aetiological factor. The condition appears common enough to form a significant group of glaucoma patients and to be a separate clinical entity.

Fluorescein angiography and fluorophotometry of the iris in pseudoexfoliation of the lens capsule.

Fluorescein iris angiography and fluorophotometry were performed on a series of 9 patients with bilateral and 11 with unilateral pseudoexfoliation, 12 bilateral aphakes with pseudoexfoliation, and 7 unilateral aphakes with bilateral pseudoexfoliation. Angiography showed a loss of radial iris vessels, a heavy leak of fluorescein from the pupil margin, progressive neovascularisation of the outer 2/3 of the iris, and less constantly a network of fine new vessels in the inner 1/3 of the iris stroma. These changes were absent in unaffected eyes. After cataract extraction there seemed to be a definite lessening of fluorescein leak from the pupil margin. Fluorophotometry showed a much higher fluorescein concentration at the anterior focus in eyes with pseudoexfoliation than in normal controls or in fellow unaffected eyes. There was a much smaller rise in fluorescein concentration at the posterior focus in a minority of affected eyes. The ranges of fluorescein concentrations at the anterior focus in both phakic and aphakic patients with bilateral pseudoexfoliation did not differ significantly. The concentration at the anterior focus of unilateral aphakes with bilateral pseudoexfoliation was lower than in the fellow phakic eye. These findings suggest that the neovascular reaction seen in pseudoexfoliation is associated with patchy occlusion of the normal iris vasculature, occurs in the anterior segment of the eye, and does not continue to progress after removal of the lens.

Spontaneous orbital haemorrhage.

A 57-year-old housewife, with controlled hypertension, presented with acute right proptosis and visual loss with external ophthalmoplegia due to spontaneous orbital haemorrhage. Vision and ocular motility were returned to normal by the rapid surgical evacuation of the blood. Acute orbital haemorrhage is an ocular emergency requiring urgent treatment to prevent the usual previously reported outcome of permanent visual loss.

Progressive myopia in early onset chronic angle closure glaucoma.

A 19-year-old girl presented with advanced unilateral chronic angle closure glaucoma and myopia with gross cupping and field loss in a previously hyperopic eye with a marked increase in corneal curvature. This emphasises that a marked myopic shift may be an important sign of glaucoma in a young patient.

Occurrence of malignant glaucoma after laser iridotomy.

A case is described of malignant glaucoma with extreme shallowing of the anterior chamber (AC) and an abnormally high intraocular pressure (IOP) following laser iridotomy for acute angle closure glaucoma. The episode followed the use of strong miotic (pilocarpine hydrochloride 4%) and was reversed by mydriatics including phenylephrine hydrochloride. Serial estimation of anterior chamber depth is important in the management of angle closure glaucoma.

Tolerance of the eye for implanted cilia.

Retained cilia in the eye following injury are rare. There are reports of long term tolerance to cilia in the anterior chamber but no information about the effect on the corneal endothelium. A 31-year-old man was seen with a 19-year history of a retained eyelash embedded in a corneal scar and extending across the anterior chamber to the chamber angle. The follicle was absent. There was no cellular inflammatory reaction, and the eye otherwise appeared normal on slit-lamp examination with normal vision. However, there was the appearance of an encrusted deposit on the surface of the lash and a markedly lowered endothelial cell count of 750 cells/mm2 compared with the fellow eye. The lash was not removed.