Immune response to specific molecules of the retina in proliferative vitreoretinal disorders

In recent years, several reports have contributed to a growing suspicion that there is immunologic involvement in proliferative intraocular disorders such as proliferative vitreoretinopathy and proliferative diabetic retinopathy. Immune privilege, as in the brain, ovary and testis, also exists in the eye. Therefore, immune responses to unique molecules of the eye, e.g. retinal S-antigen (S-Ag), which the immune system never learns to regard as self, are possible. This study describes the presence of S-Ag, a major soluble photoreceptor protein involved in the visual transduction cascade, in pathological vitreous. We employed indirect immunoblotting, with human retina as substrate, and demonstrated the occurrence of antiretinal antibodies in the sera of a series of patients with proliferative vitreoretinal disorders. Immunoblot analysis of physiological retina and lyophilized S-Ag, revealed this protein as a target molecule of the immunological involvement of the retina. Further immunochemical investigation, however, must clarify whether this autoimmune reaction is the cause, a consequence, or an aggravating factor of the disease. As we come to understand the cellular and molecular mechanism, a new generation of therapeutic strategies may be envisioned.Presented in part at the 18th Meeting of the Club Jules Gonin, Vienna, 1992     

Mesenteric cystic neoformations: Report of two cases

(Received for publication on Apr. 28, 1997; accepted on May 15, 1998)     

National Surveillance System and Hib meningitis incidence in Italy

In 1994, the Italian Ministry of Health implemented a National Surveillance System to obtain data on the incidence of bacterial meningitis and its causative agents, including Haemophilus influenzae type b (Hib). As a consequence, case reporting of Hib meningitis is increasing year by year; in 1996, there were 126 notifications, of which 73% were in children under 2 years of age. Although underreporting still exists, parallel prospective or retrospective epidemiological surveys conducted in some Italian Regions allowed for partial correction of the incidence of Hib meningitis (up to 18.5/100,000 population in 1994).     

Vertical subcutaneous pedicle flaps for posterior perineal reconstruction

PURPOSE: Loss of a certain amount of cutaneous tissue of the perineal region may be remedied by first intention with creation of cutaneous flaps, thus preventing second intention healing. METHODS: We present three emblematic cases in which the posterior perineal region was reconstructed by means of vertical subcutaneous pedicle flaps, subsequent to cutaneous tissue loss after surgery for extensive condilomas or neoplastic pathologies. RESULTS: Tissue loss was repaired by means of a V-Y type vertical subcutaneous pedicle flap, constructed laterally of the extirpation zone and advanced in a median direction. In all cases, no ischemia or infection of flaps occurred; sphincteral continence and long-term aesthetic results have proved to be satisfactory. CONCLUSIONS: Vertical pedicle subcutaneous flaps are well vascularized, extremely mobile, and easy to perform and have no serious postoperative complications.     

Physicians and death: Comments and behaviour of 605 doctors in the north-east of Italy

The aim of this study was to determine the influence of socio-demographic and professional factors on physicians' attitudes to the terminally ill. Between May 1992 and May 1993, a survey was conducted in the province of Pordenone (north-east, Italy) in order to analyse a number of specific issues, such as emotional involvement, the need for aggressive treatments and the communication of diagnosis and prognosis. After obtaining a list of board-certified physicians from the Medical Association office in Pordenone, a modification of the cancer questionnaire of Haley and Blanchard (QSPT) was mailed to 916 doctors. Of these, 605 (60%; 487 male, 118 female; mean age 41 ± 11 SD) returned the completed questionnaire. Within the group of responders, we identified three main subgroups, according to their type of activity: general practitioners (175, 29%), hospital doctors (235, 39%) and other doctors (195, 32%). In age, sex and activity, the only significant difference between responders and non-responders was age (mean age 41 and 43 years respeetively). Most of the responders (77%) stated that they were able to deal with the terminally ill patient and his/her needs; 44%, however, admitted that patients' anxiety is sometimes unbearable. For the vast majority of the doctors polled (91%), providing a comfortable environment for an incurable patient was more important than pursuing aggressive treatment, but only 44% were convinced of the uselessness of aggressive care. To the question on whether to disclose information about imminent death to allow patients to prepare spiritually, 37% answered No, 38% Yes, and 25% were uncertain. Almost all responders (95%), however, believed in the beneficial effect of hope on the terminally ill. Ourresults suggest that doctors' professional and, most of all, sociodemographic and cultural factors determine the relationship with the patient on both the emotional and the clinical decision-making levels.     

Adenosine coronary vasodilation quantitative technetium 99m methoxy isobutyl isonitrile myocardial tomography in the identification and localization of coronary artery disease

Background

Exercise and dipyridamole ^99mTc-labeled methoxy isobutyl isonitrile (MIBI) myocardial scintigraphy have been widely used for the diagnosis of coronary artery disease (CAD). However, only limited data on adenosine ^99mTc-labeled MIBI cardiac imaging are currently available. This study was designed to assess the accuracy of quantitative adenosinerest ^99mTc-labeled MIBI tomography in the diagnosis and localization of CAD.

Methods and Results

Fifty-seven consecutive patients with suspected CAD who underwent coronary angiography and 22 normal volunteers were studied. All patients underwent ^99mTc-labeled MIBI tomography after administration of adenosine (140 μg/kg intravenously for 6 minutes) and at rest. A total of 171 vascular coronary territories were analyzed quantitatively. All patients with CAD (≥50% luminal stenosis) (n=55) had abnormal ^99mTc-labeled MIBI tomograms. The normalcy rate was 86% by quantitative analysis. Overall sensitivity, specificity, and diagnostic accuracy for detection of individual stenosed vessels were 84%, 87%, and 85%, respectively. In patients with one-vessel CAD (n=24), sensitivity and diagnostic accuracy in the detection of individual stenosed vessels were significantly (p<0.05) higher compared with patients with multivessel CAD (n=31). Moreover, 75% of patients with one-vessel disease showed a scintigraphic pattern characterized by the presence of perfusion defects in only one coronary artery territory, and 74% of patients with multivessel disease showed a scintigraphic pattern characterized by the presence of perfusion defects in two or more coronary artery territories. Sensitivity, specificity, and diagnostic accuracy for detecting individual diseased vessels were similar in patients without previous myocardial infarction (n=18) compared with those with previous myocardial infarction (n=39). In myocardial territories related to noninfarcted areas (n=124), sensitivity and specificity in the detection of stenosed vessels were 75% and 88%. In infarcted areas (n=47), sensitivity and specificity in the detection of stenosed vessels were 98% and 80% (differences not significant vs noninfarcted areas).

Conclusions

Adenosine-controlled coronary vasodilation combined with quantitative ^99mTc-labeled MIBI tomography is accurate for identifying patients with CAD and localizing individual stenosed coronary arteries.     

Quantitative exercise technetium-99m tetrofosmin myocardial tomography for the identification and localization of coronary artery disease

The aim of this study was to evaluate the accuracy of quantitative 1-day exercise-rest technetium-99m tetrofosmin tomography in the identification of patients with coronary artery disease (CAD) and in the detection of individual stenosed coronary vessels. Sixty-one patients with suspected CAD who underwent coronary angiography and 13 normal volunteers were studied. All patients were submitted to two i.v. injections of^99mTc-tetrofosmin, one at peak exercise (370 MBq) and the other (1110 MBq) at rest 3 h after exercise (images 15–30 min after injection for both studies). All patients with CAD (0% luminal stenosis) (n=50) had an abnormal^99mTc-tetrofosmin tomogram. Only one patient without significant coronary narrowing showed abnormal findings. Overall sensitivity, specificity and diagnostic accuracy in the detection of individual stenosed vessels were 77%, 93% and 85%, respectively. Sensitivity and diagnostic accuracy in the identification of individuals stenosed coronary vessels were significantly higher (P<0.05) in patients with single-vessel disease (n=21) than in those with multivessel disease (n=29). Sensitivity, specificity and accuracy for detecting individual diseased vessels were similar in patients without previous myocardial infarction (n=26) and in those with previous myocardial infarction (n=35). In myocardial territories related to non-infarcted areas (n=128), sensitivity and specificity in the detection of stenosed vessels were 70% and 95%, respectively. In infarcted areas (n=55), sensitivity and specificity in the detection of stenosed vessels were 85% (P=NS vs non-infarcted areas) and 75% (P<0.05 vs non-infarcted areas), respectively. Finally, sensitivity was significantly lower (P<0.05) in vascular territories supplied by vessels with moderate stenosis (50%–75%) than in those supplied by vessels with severe stenosis (>75%). The results of this study demonstrate that quantitative 1-day exercise-rest^99mTc-tetrofosmin single-photon emission tomographic imaging is a suitable and accurate technique to identify patients with CAD and to detect individual stenosed coronary vessels.     

Studies of fragmented sarcoplasmic reticulum from human skeletal muscle.

Sarcoplasmic reticulum (SR) vesicles were isolated from muscle biopsies of 4 normal volunteers, a patient with McArdle disease (before and during contracture), and a patient with normokalemic periodic paralysis. Fractions were analyzed for purity by electron microscopy and biochemical analysis of specific marker enzymes. Adenosine triphosphate (ATP)-dependent calcium ion uptake was measured kinetically by the absorbence changes of murexide, a metallochromic indicator of ionized Ca++ concentrations, in the absence of oxalate or other calcium-complexing anions. In these experiments, time resolution of the Ca++ transport rate was limited by the manual mixing of reagents, which occurred in 1 to 3 seconds. In 1 case the "true" initial velocity of Ca++ uptake was measured by rapid mixing of ATP in a stopped-flow apparatus and by following the change in absorbence of murexide in a storage oscilloscope. In SR from normal human muscle the ATP-dependent Ca++ uptake was 3.5 nmoles per second per milligram of protein for the first 5 seconds after ATP mixing. Fast kinetic experiments showed that Ca++ uptake proceeded linearly for the first 500 msec at a rate of 9 nmoles per second per milligram of protein (at 25 degrees C) and then progressively declined to reach steady-state levels in 40 to 50 seconds. No abnormality of Ca++ transport was found in SR vesicles from the patient with McArdle disease and the patient with normokalemic periodic paralysis.     

Late-onset acid maltase deficiency. Detection of patients and heterozygotes by urinary enzyme assay.

Daily urinary excretion of acid maltase (12.78 +/- 2.10 units/24 hr/mg of creatinine, in 11 normal adults) was significantly decreased in ten patients with late-onset acid maltase deficiency (1.33 +/- 0.16 units/24 hr; P less than .001) and 11 heterozygotes (3.27 +/- 0.62 units/24 hr; P less than .001). Maximal inhibition of urinary acid maltase activity by antibodies against human placental enzyme was 53% in controls, 30% in heterozygotes, and virtually absent in patients. Investigation of pH curves and enzyme inhibition by antibodies confirmed the presence in the kidney of an immunologically distinct "extra" maltase enzyme active at acid pH. Whether acid maltase in normal urine originates in the kidney or cells of the lower urinary tract, the enzyme defect seems to be expressed in these cells in late-onset acid maltase deficiency.