Exaggerated relative nasal-temporal asymmetry of macular capillary blood flow in patients with clinically significant diabetic macular oedema.

AIMS: To compare the macular capillary blood flow of patients with clinically significant diabetic macular oedema (DMO) with that of non-diabetic subjects and to determine the relation between blood flow and capillary leakage in patients with DMO. METHODS: The sample comprised 45 non-diabetic subjects (mean age 59 years) and 18 type 2 patients with clinically significant DMO (mean age 60 years). Macular capillary blood flow measurements were acquired using the Heidelberg retina flowmeter (HRF) and a 10 degrees x2.5 degrees scan field centred on the fovea. Fluorescein angiography was undertaken on each of the diabetic patients after the completion of HRF measurements. RESULTS: Temporal macular capillary blood flow was significantly lower for the patients with clinically significant DMO compared with age matched non-diabetic subjects (ANCOVA, p = 0.0011) while relative nasal-temporal asymmetry of macular capillary blood flow was significantly higher (p = 0.0125). Nasal-temporal asymmetry of macular capillary blood flow was significantly higher for the patients with DMO and capillary leakage within the scan area (two tailed t test, p = 0.0071). Macular capillary blood flow was always lower in areas of DMO and capillary leakage. CONCLUSION: Capillary blood flow was reduced in areas of DMO and capillary leakage, suggesting the presence of a localised perturbation of capillary blood flow regulation.

Bleomycin-induced pulmonary function abnormalities.

The usefulness of serial PFTs in identifying patients who are developing BIP was assessed in 59 men with non-seminomatous testicular carcinoma. The mean age was 27.7 years and all the patients received a standard three-course chemotherapy regimen consisting of vinblastine, bleomycin, and cis-diamminedichloroplatinum. The average dose of bleomycin was 555.5 units. Serial PFTs, chest roentgenograms, and medical assessments were done prior to each course of bleomycin. Nine (15.3 percent) patients developed pulmonary symptoms due to bleomycin and 23 (39 percent) had significant changes on chest x-ray films. The Dsb dropped significantly with bleomycin treatment; therefore, it is the most sensitive indicator of pulmonary response to bleomycin. However, the Dsb failed to differentiate patients with BIP from those without. The TLC was found to be a much more specific indicator of BIP because reduction in TLC correlated with the development of pulmonary symptoms and roentgenologic changes.

Changes in hospital admissions pattern in patients with human immunodeficiency virus infection in the era of Pneumocystis carinii prophylaxis.

BACKGROUND: Pneumocystis carinii pneumonia (PCP) was the leading cause of hospital admissions in patients with human immunodeficiency virus (HIV) infection before the widespread use of PCP prophylaxis. We studied retrospectively the changes in annual hospital admission patterns after the start of a population-based PCP prophylaxis program in Toronto. The purpose of the study was to identify the cogent diseases requiring hospitalization of HIV patients in the current era of PCP prophylaxis. This information is important for the allocation of health care resources in the future as well as for targeting research in the prevention of specific HIV-related diseases. METHODS: The annual HIV-related hospital admissions before and after the start of the Toronto aerosol pentamidine program (May 1989) were studied. All admission records due to AIDS-defining illnesses or occurring in patients with known HIV status in three major referral centers were reviewed. The two periods for comparison were May 1988 through April 1989 and May 1989 through April 1990. The data obtained were stratified according to the following: (1) cause of the illness prompting hospital admission; (2) PCP admissions; and (3) admissions according to the major organ system involved. These categoric data were compared by nonparametric chi 2 tests. RESULTS AND CONCLUSIONS: Population-based prophylaxis of PCP with aerosol pentamidine resulted in a significant reduction in the total number of PCP hospital admissions. Infection remains the principal cause of hospital admission in HIV patients after the start of the PCP prophylaxis program. However, there was an increase in the proportion of hospital admissions due to nonrespiratory-related infections. There was also a modest increase in admissions due to neurologic and gastrointestinal diseases. Central nervous system lymphoma and cytomegalovirus retinitis accounted for the majority of the rise in the nervous system. These data suggest there is a changing pattern of the diseases leading to the hospitalization of patients with HIV infection in the era of PCP prophylaxis.

Intraocular and interocular symmetry in normal retinal capillary perfusion.

PURPOSE: To investigate retinal capillary perfusion in different areas of the posterior pole (intraocular symmetry) and to compare capillary perfusion between the right and left eyes (interocular symmetry). METHODS: The study consisted of 52 clinically healthy patients between the ages of 45 and 74 years. Good quality images were obtained in 30 patients. By using scanning laser Doppler flowmetry with the Heidelberg Retina Flowmeter, three 10 degree scans were obtained from the fovea and superior and inferior retina of the study eye (for intraocular symmetry) and from the fovea of the fellow eye (for interocular comparison). Values of volume, flow, and velocity were recorded from each of these areas. Repeated measures analysis of variance, with Bonferroni correction, was used for groupwise comparison between areas in the study eye. Paired t tests, with Bonferroni correction, were used to compare nonfoveolar perfusion between the right and left eyes for each patient. RESULTS: Capillary volume in the foveola was significantly less than that in areas superior and inferior and 3 degrees nasal and temporal, and it was found to increase with eccentricity in the macular region. Only 2 of 30 patients had significant interocular differences between the extrafoveolar areas. CONCLUSION: Significant differences in retinal capillary perfusion were found across the macular region and corresponded with the increase in capillary beds. The Heidelberg Retina Flowmeter also measured the expected decrease in volume at the foveolar avascular zone. There were no significant interocular differences in perfusion. Eye movements, media opacities, and poor tear film quality had a deleterious effect on image quality.

Inflammation-mediated retinal edema in the rabbit is inhibited by topical nepafenac.

The purpose of this study was to evaluate the ability of the nonsteroidal anti-inflammatory drug nepafenac to prevent development of mitogen-induced pan-retinal edema following topical ocular application in the rabbit. Anesthetized Dutch Belted rabbits were injected intravitreally (30 microg/20 microL) with the mitogen concanavalin A to induce posterior segment inflammation and thickening (edema) of the retina. The Heidelberg Retina Tomograph was used to generate edema maps using custom software. Blood-retinal barrier breakdown was assessed by determining the protein concentration in vitreous humor, whereas analysis of PGE2 in vitreous humor was performed by radioimmunoassay. Inhibition of concanavalin A-induced retinal edema was assessed 72 h after initiation of topical treatment with nepafenac (0.1-1.0%, w/v), dexamethasone (0.1%), VOLTAREN (0.1%), or ACULAR (0.5%). Concanavalin A elicited marked increases in vitreal protein and PGE2 synthesis at 72 h postinjection. Retinal thickness was also increased by 32%, concomitant with the inflammatory response. Topical application of 0.5% nepafenac produced 65% reduction in retinal edema which was correlated with 62% inhibition of blood-retinal barrier breakdown. In a subsequent study, 0.5% nepafenac significantly inhibited (46%) blood-retinal barrier breakdown concomitant with near total suppression of PGE2 synthesis (96%). Neither Voltaren nor Acular inhibited accumulation of these markers of inflammation in the vitreous when tested in parallel. This study demonstrates that nepafenac exhibits superior pharmacodynamic properties in the posterior segment following topical ocular dosing, suggesting a unique therapeutic potential for a variety of conditions associated with retinal edema.

Community acquired, nursing home acquired and hospital acquired pneumonia: A five-year review of the clinical, bacteriological and radiological characteristics.

PURPOSE: To assess the contemporary clinical, bacteriological and radiographic features of hospitalized patients with community acquired (ca), nursing home acquired (na) and hospital acquired pneumonia (ha) and to examine patient outcome. PATIENTS AND METHODS: All hospital records of patients with pneumonia over a five-year period from April 1987 to March 1992 were reviewed retrospectively. Patients included in the study were all those with a diagnosis of pneumonia as identified by computer records of diagnostic codes at discharge; patients with a specific diagnosis of Pneumocystis carinii pneumonia were excluded. Of 74,435 discharges over the five-year period, 1782 patients met the inclusion criteria. RESULTS: Charts of 1622 of the total 1782 cases were reviewed. Mean age was 64.4 years with 59.4% men and 40.6% women. Sixty-three per cent were ca, 28.5% were ha and 8.5% were na. A total of 1542 patients (95%) had at least one concomitant medical condition. Chest roentgenogram was abnormal in 97%. Common organisms isolated overall were Haemophilus influenzae (from 204 patients), Staphylococcus aureas (from 152 patients), Streptococcus pneumoniae (from 143 patients ), Escherichia coli (from 113 patients) and Pseudomonas aeruginosa (from 111 patients). H influenzae and S pneumoniae were most common in ca pneumonia, whereas S aureus and Gram-negative organisms were more common in the ha group and Gram-negative agents in the na group. One hundred and four patients developed complications. Fifteen per cent required intensive care unit admission. The average length of hospitalization in the ca and na groups was 17 days and in the ha group, 43 days. At time of discharge 1261 patients (78%) were cured or improved, and 361 patients (22%) died during the admission. CONCLUSIONS: These results suggest that hospitalization for pneumonia in the 1990s is primarily for elderly patients with significant co-morbidity. Although microbiology appears unchanged compared with earlier reports, the contemporary population is significantly sicker than previous cohorts. This may account for the persistently high morbidity and mortality despite better or newer antibiotics.

A prospective comparison of Porta-sonic and Fisoneb ultrasonic nebulizers for administering aerosol pentamidine.

OBJECTIVE: To report patient acceptability and overall therapeutic effectiveness of two different ultrasonic nebulizers, Fisoneb and Porta-sonic, for the administration of aerosol pentamidine for Pneumocysitis carinii prophylaxis in human immunodeficiency virus (hiv)-infected individuals. DESIGN: Prospective assessment of a random subgroup of 174 individuals from an inception cohort of 1093 patients attending a central aerosol pentamidine treatment centre in Toronto, Ontario. METHODS: One hundred and seventy-four patients who had been receiving aerosolized pentamidine for more than 10 weeks using Fisoneb at 60 mg every two weeks were switched to Porta-sonic. Subjective evaluation included three standard 10 cm visual analogue scales rating cough/wheeze, aftertaste and overall preference. The individuals were also asked to compare the duration of time spent on the aerosol treatments. Objective evaluation included spirometry performed immediately before and 15 mins after pentamidine administration. Prospective surveillance of the entire cohort was preformed to record and document episodes of breakthrough P carinii pneumonia. RESULTS: Porta-sonic was the overall preferred nebulizer in 82% of patients. Less time was spent on aerosol treatment using the Porta-sonic nebulizer compared with the Fisoneb in 66% of patients. The Porta-sonic nebulizer system produced less aftertaste compared with Fisoneb. Both nebulizers produced significant but modest reduction in flow rates. During the study period there was no statistically significant difference in the rates of breakthrough P carinii pneumonia between the two groups. A total of 91 episodes occurred, at a rate of 0.5 episodes per patient-month on Porta-sonic compared with 0.7 episodes per patient-month on Fisoneb (P=0.2536). DISCUSSION: Aerosol pentamidine remains the proven second-line prophylaxis against P carinii pneumonia in hiv/aids for those intolerant to trimethoprim-sulphamethoxazole. Cough, bronchospasm and poor taste are side effects that may limit patient tolerance and acceptability. The results of this study show that the Porta-sonic nebulizer system significantly reduces some of these side effects and increases patient preference. CONCLUSION: This study suggests that Porta-sonic, the newer nebulizer system, with more ideal in vitro characteristics may become a favoured device in clinical practice.

The long-term effects of aerosol pentamidine on pulmonary function. The Toronto Aerosolized Pentamidine Study (TAPS) Group.

Aerosolized pentamidine (AP) has been widely used for prophylaxis of pneumocystis carinii pneumonia (PCP) since 1988. The objective of this study was to evaluate the long-term effects of AP on pulmonary function. Of 36 patients with AIDS who were receiving AP for secondary prophylaxis of PCP, 13 patients had been using AP continuously for more than 52 weeks. AP was given using a Fisoneb ultrasonic nebulizer with five loading doses of 60 mg over two weeks, followed by one dose of 60 mg every two weeks. Baseline PFT were TLC 92 +/- 14% pred, FVC 90 +/- 11% pred, FEV1 91 +/- 11% pred, FEF25-75 95 +/- 17% pred, and DLCO (corrected for hemoglobin) 70 +/- 22% pred. No significant change in TLC, FVC, FEV1, or DLCO was seen after 56 weeks of AP. There was a 20% fall in FEF25-75 seen after 56 weeks, which was statistically significant. However, the clinical significance of a fall of this magnitude in the FEF25-75 is uncertain. Similar results were seen in a smaller subset of patients who received AP for at least 76 weeks. Although the small sample size must be considered, this data suggests that there is no clinically significant change in pulmonary function associated with the use of AP for up to 76 weeks.

Current trends in HIV-related hospital admissions and their impact on hospital resource utilization in Ontario.

OBJECTIVE: To assess changes in patterns of hospital admissions, in frequency of admissions and in average length of stay (ALOS) at a tertiary HIV referral centre, and to investigate the overall impact of care for patients with HIV infection of AIDS on peer hospitals in Ontario. DESIGN: Descriptive study. PARTICIPANTS: Data were obtained on patients with HIV infection or AIDS treated at the Wellesley Hospital in Toronto for the fiscal years (May 1 to Apr. 31) 1990-91, 1991-92 and 1992-93, and on admissions for HIV or AIDS in 9 peer hospitals in Ontario during the same period. INTERVENTIONS: For the Wellesley Hospital, review of medical records of HIV-related admissions to determine the reasons for admission and to examine concurrent illnesses. For the Wellesley Hospital Hospital and peer hospitals, analysis of changes in ALOS and Resource Intensity Weights (RIWs). RESULTS: Between May 1, 1990, and Apr. 31, 1993, the number of admissions for treatment of Pneumocystis carinii pneumonia (PCP) fell, but admissions for respiratory infections other than PCP remained very common, although they decreased slightly. Overall, infection remained the main reason for admission. The frequency of gastrointestinal complications necessitating admission increased. The frequency of admissions remained high, although the ALOS decreased significantly. In the period between Apr. 1, 1991, and Mar. 31, 1994, the proportion of HIV-related discharges and total hospital discharges among the 9 peer hospitals remained stable. The HIV-related ALOS decreased substantially. Although the HIV-related average RIW decreased slightly, this measure and the mortality rate are still much higher for HIV-related admissions than for overall admissions. CONCLUSIONS: This contemporary survey suggests that nonrespiratory infection complications have become the main reason for admission of patients with HIV infection or AIDS, but that the HIV tertiary hospitals are coping with the load of HIV-related admissions and the high average RIW associated with these patients by reducing the ALOS.