Resolution of focal fatty infiltration of the liver

Focal fatty infiltration of the liver has been recognized as a distinct entity only since 1980. It may simulate neoplastic or other low-density parenchymal lesions, including abscesses and hemangiomas. I report a case of histologically confirmed focal fatty infiltration of the liver in a man with obesity and alcoholism; the lesion disappeared after the patient began a program of exercise, weight loss, and abstinence from alcohol. The possible pathogenesis of focal fatty infiltration of the liver is reviewed, diagnostic techniques are described, and reversibility of the lesion is discussed.     

Molecular typing shows a high level of HLA class I incompatibility in serologically well matched donor/patient pairs: implications for unrelated bone marrow donor selection

In comparison with HLA-matched sibling bone marrow transplants, unrelated donor transplants are associated with increased graft-versus-host disease and graft failure. This is likely in part due to HLA incompatibilities not identified by current matching strategies. High resolution DNA-based typing methods for HLA class II loci have improved donor selection and treatment outcome in unrelated donor bone marrow transplantation. By using DNA-based typing methods for HLA-A and -B on a cohort of 100 potential bone marrow donor/patient pairs, we find that serological typing for HLA class I is limited in its ability to identify incompatibilities in unrelated pairs. Furthermore, the incompatibilities identified are associated with the presence at high frequency of alloreactive cytotoxic T-lymphocyte precursors. DNA typing also indicates that HLA-C mismatches are common in HLA-A and -B serologically matched pairs. Such mismatches appear to be significantly less immunogenic with respect to cytotoxic T-lymphocyte recognition, but are expected to influence natural killer cell activity. Thus, improved resolution of HLA class I shows many previously undisclosed mismatches that appear to be immunologically functional. Use of high resolution typing methods in routine matching is expected to improve unrelated donor selection and transplant outcome.     

Differences in psychosocial and health correlates of major and minor depression in medically ill older adults

OBJECTIVES: To compare the differences in correlates of different levels of depression in medically ill hospitalized older adults. DESIGN, SETTING, AND PARTICIPANTS: A consecutive series of 542 patients aged 60 or older admitted to the medical inpatient services of Duke Hospital underwent a structured psychiatric evaluation administered by a psychiatrist. MEASUREMENT: A wide range of demographic, social, psychiatric, and physical health data were collected, and associations with major and minor depression were assessed. RESULTS: Compared with patients without depression, those with major depression were more likely to have a history of prior episodes of depression, higher dysfunctional attitude scores, greater overall severity of medical illness, cognitive impairment, and symptoms of pain or other somatic complaints. Specific medical diagnosis was less important a predictor of major depression than overall severity of medical illness. Compared with patients without depression, those with minor depression were more likely to report non-health-related stressors during the year before hospital admission, have a diagnosis of immune system disorder, and have greater severity of medical illness. When major and minor depression were compared directly, on the other hand, no significant differences were observed except for history of depression, and that relationship was weak and present only when the etiologic approach to diagnosis was used. CONCLUSION: During hospital admission, certain psychosocial, psychiatric, and physical health characteristics of older medical patients place them at high risk for different levels of depression. Patients with major and minor depression resemble each other more than they do patients without depression. These findings may help clinicians better understand the causes of different types of depression in this setting and lead to improved diagnosis and treatment.     

Effects of changes in intraocular pressure on human ocular haemodynamics

PURPOSE: Myogenic autoregulation is the ability of a vascular bed to maintain blood flow despite changes in perfusion pressure. Ocular perfusion pressure is defined as the difference between ocular arterial pressure and ocular venous pressure, the latter dependent on intraocular pressure (IOP). The aim of the present study was to investigate the effect of moderate increases in IOP on ocular haemodynamics. METHODS: Changes in IOP (+ 10 mmHg, +20 mmHg) were induced by a suction cup in 10 healthy subjects. Ocular fundus pulsations in the macula and the optic disc were measured by laser interferometry; blood flow velocities in the central retinal artery (CRA) and in the ophthalmic artery (OA) were measured by Doppler sonography. RESULTS: Changes in IOP caused a significant reduction in fundus pulsations, which was more pronounced in the macula (at +10 mmHg: -9 +/- 2%, p < 0.01; at +20 mmHg: -19 +/- 3%, p < 0.001) than in the optic disc (at +10 mmHg: -5 +/- 2% (ns); at +20 mmHg: -9 +/- 3%, p < 0.01). Mean flow velocity in the CRA was reduced by -5 +/- 3% at +10 mmHg (ns) and by -14 +/- 5% at +20 mmHg (p < 0.005), resistive index was increased by +4 +/- 1% at +10 mmHg (p < 0.05) and by +6 +/- 2% at +20 mmHg (p < 0.01). In contrast, a rise in IOP did not affect blood flow parameters in the OA. CONCLUSIONS: Our results from fundus pulsation measurements indicate that choroidal blood flow decreases when IOP is increased. The Doppler sonographic findings in the CRA indicate reduced blood flow velocity in this artery during raised IOP.     

Correlation between ear canal resonance and tympanic membrane impedance in relation to age and body mass and postmortem changes

The human temporal bone preparation is an acknowledged model for research of the physical processes affecting the outer ear canal and eardrum. Changes affecting the oscillation and resonance behavior of the tympanic membrane and ear canal between death and temporal bone preparation presently exist in only a few studies. Since the influence of age and physique, as well as the width of ear canal on the ear canal resonance may be important, we prepared two separate studies to analyze these questions. The goal of our first test series involved children and was devised to determine if changes in the outer auditory canal resonances differed according to age. In so doing, canal resonance was recorded with a real ear measurement system. Further, we recorded middle ear pressure, impedance of the tympanic membrane, ear canal volume, height, weight and surface of the body, head and ear size. We found a significant decrease in the resonance frequency of the outer ear which was age-dependent and was 2.75 kHz in the 7-year-old child. In a separate study we wanted to know if results found in the postmortem temporal bone reflected in vivo relationships. A tympanometer and real ear measurement system was used to test the resonance behavior of the auditory canal as well as the vibration of the eardrum in dependence on temperature and the time after death for 9 h. We then proved the absence of significant changes in the auditory canal and eardrum oscillation in this time period before possible postmortem changes occurred. Our findings show that the method of bone preservation after its preparation is decisive for the validity of measurements in the isolated human temporal bone.     

Elastin degradation by matrix metalloproteinases. Cleavage site specificity and mechanisms of elastolysis

Insoluble elastin was used as a substrate to characterize the peptide bond specificities of human (HME) and mouse macrophage elastase (MME) and to compare these enzymes with other mammalian metalloproteinases and serine elastases. New amino termini detected by protein sequence analysis in insoluble elastin following proteolytic digestion reveal the P'1 residues in the carboxyl-terminal direction from the scissile bond. The relative proportion of each amino acid in this position reflects the proteolytic preference of the elastolytic enzyme. The predominant amino acids detected by protein sequence analysis following cleavage of insoluble elastin with HME, MME, and 92-kDa gelatinase were Leu, Ile, Ala, Gly, and Val. HME and MME were similar in their substrate specificity and showed a stronger preference for Leu/Ile than did the 92-kDa enzyme. Fibroblast collagenase showed no activity toward elastin. The amino acid residues detected in insoluble elastin following hydrolysis with porcine pancreatic elastase and human neutrophil elastase were predominantly Gly and Ala, with lesser amounts of Val, Phe, Ile, and Leu. There were interesting specificity differences between the two enzymes, however. For both the serine and matrix metalloproteinases, catalysis of peptide bond cleavage in insoluble elastin was characterized by temperature effects and water requirements typical of common enzyme-catalyzed reactions, even those involving soluble substrates. In contrast to what has been observed for collagen, the energy requirements for elastolysis were not extraordinary, consistent with cleavage sites in elastin being readily accessible to enzymatic attack.