Abnormal neuromuscular junctions in the lateral rectus muscle of wobbler mice

We have studied the lateral rectus muscles and neuromuscular junctions (NMJs) of abducens motoneurons in wobbler (wr/wr) mutant mice from 26 to 58 days of age. The muscles of wr/wr weighed about 70% of the weight of littermate controls and were composed of fiber types comparable to those of controls, as assayed by succinate dehydrogenase activity. The most obvious difference between wr/wr and control NMJs was a reduction in the length of the postjunctional membrane of wr/wr mice. The mutant muscle endplate membrane was only about 70% (6.58 micron) the length of control muscle regions (9.44 micron). There were no obvious differences at the light microscopic level in the distribution of acetylcholine (ACh) receptors at junctional regions or staining of acetylcholinesterase, as assayed with alpha-bungarotoxin binding or enzyme histochemistry. Indirect immunocytochemical studies using antibodies directed against the subunits of the ACh receptor failed to indicate an abnormal presence of immature receptors clustered at the NMJs of wr/wr mice. Our findings suggest that the formation or maintenance of normal postjunctional folds and the differentiation of receptors at the junctions are under independent control during development. Furthermore, the wobbler mutation may affect muscle cell differentiation as well as neuronal differentiation. This mutant mouse should prove a useful model for study of postjunctional fold formation and function.     

Alpha-1-antichymotrypsin in renal biopsies

Alpha 1-Antichymotrypsin (alpha 1-AK) and alpha-1-antitrypsin (alpha 1-AT) represent a defense mechanism to protect the tissues from proteolytic enzyme activity. We studied the implication of alpha 1-AK and alpha 1-AT in glomeruli of patients with different nephropathies based on the analysis of 52 paraffin-embedded renal biopsies with alpha 1-AK and alpha 1-AT antisera. The results demonstrate an intense alpha 1-AK glomerular staining in renal biopsies from patients with minimal-change disease, while a minor staining of this protein was found in the other nephropathies. No significant evidence of alpha 1-AT deposits was observed in our cases. Our findings suggest that when alpha 1-AK is lacking in glomeruli the defense mechanisms against proteolytic enzymes may not be efficient enough to protect the glomerular structures and limit the damage. Since alpha 1-AK is a reactant of the acute phase of inflammation, it may be considered as a marker of activity for monocyte-macrophages in glomerular damage.     

Perinatal and infant mortality rates and place of birth in Italy, 1980.

In 1980, the ratio of home birth to public hospital perinatal and neonatal mortality rates decreased from Northern to Southern Italy, being inversely related to the proportion of home deliveries and probably reflecting the effect of planned versus unplanned home births. The post neonatal mortality rate in Southern Italy was about four times as high in children born at home (9.5/1,000 live births) than in those delivered in public hospitals (2.6/1,000 live births), probably reflecting differences in the socioeconomic status according to the birthplace selection in various regions.     

Pancreas and kidney transplantation: the San Raffaele Hospital (Milan, Italy) experience

Results of 33 simultaneous pancreas and kidney transplantations performed at the San Raffaele Hospital, Milan, Italy are presented. In 26 cases segmental neoprene duct-injected grafts were transplanted and in seven cases, duodenopancreatic bladder-drained grafts. Five-year patient, kidney and pancreas survival were respectively, 89%,72% and 58%. Five-year survival in patients with technically successful pancreas transplants was 73%. Thrombosis occured in 20% of cases. Mortality was 6% and overall morbidity 76%. Surgical complications were present in 51% of cases.     

Mood state and cerebral metabolism in persons with age-associated memory impairment

People undergoing medical procedures sometimes experience feelings that may influence the results. In this study, we explore the relationship between changes in mood state self-ratings and cerebral glucose metabolism during positron emission tomography (PET) in persons with age-associated memory impairment (mean age 59.4±9.8 years). Brain regions of interest involved in both mood and memory were examined. Mood ratings of increased boredom correlated significantly with mesial temporal and parietal asymmetry and decreased parietal metabolism. Mood ratings of increased fatigue correlated with basal ganglia asymmetry and the right basal ganglia and left mesial temporal metabolism. These findings suggest that subjective mood state changes during PET may influence metabolism in brain regions implicated in emotion and memory function in people with age-related memory complaints.     

Indomethacin-Dipalmitoylphosphatidylcholine Interaction. A Calorimetric Study of Drug Release from Poly(Lactide-co-glycolide) Microspheres into Multilamellar Vesicles

A comparative study of indomethacin controlled release from poly(lactide-co-glycolide) (50:50, molecular weight 3000) (PLGA) microspheres loaded with two different amounts of drug (10.9 ± 1%, and 34.1 ± 1% w/w) and pure free indomethacin, considering the effects exerted by the drug on the thermotropic behavior of dipalmitoylphosphatidylcholine multilamellar vesicles, was carried out by differential scanning calorimetry (DSC). The release was monitored by comparing the effect exerted by the free indomethacin on lipid thermotropic behavior with that of the drug released by the microspheres and relating these effects to a lipid aqueous dispersion containing the molar ratio of drug able to cause it. By DSC measurements, the pure free indomethacin was found to be able to have a fluidifying effect on the model membrane, causing a shift toward lower values of the transitional temperature (T_m), characteristic of phospholipid liposomes, without variations in the enthalpic changes (ΔH). This shift was found to be modulated by the drug molar fraction with respect to the lipid concentration in the aqueous dispersion. Successively, calorimetric measurements were performed on suspensions of blank liposomes added to weighed amounts of unloaded and indometha-cin-loaded microspheres as well as free powdered indomethacin, and the T_m shifts of the lipid bilayer caused by the drug released from the polymeric system, as well as by the free drug, were compared with that caused by free drug increasing molar fractions dispersed directly on the membrane, employed as a calibration curve to obtain the fraction of drug released. This drug release model could be employed to determine the different kinetics involved in the drug transfer from the microspheres to a membrane. This in vitro study suggests that the kinetic process involved in drug release is influenced by the amount of drug loaded in the microspheres. This calorimetric study shows that the PLGA microspheres are a good delivery system able to sustain drug release. Moreover, the DSC technique applied to the drug interaction with biomembranes constitutes a good tool for determining the drug release representing an innovative alternative in vitro model.     

Panoramic diagnostic microhysteroscopy and female sterility: analysis of results in 284 patients

The results of panoramic diagnostic microhysteroscopy are reported in 284 patients with sterility or infertility problems. In 33.5% of the patients, microhysteroscopy revealed uterine pathology; in the majority of cases they were pathologies which are unanimously recognized as being causes of sterility, while in others there were pathologies whose role infertilities is still unclear. There was a good correlation between microhysteroscopy and histology in cases of endometrial hyperplasia and of endometritis, whereas in cases of endometrial polyps and functional diagnosis of the endometrium, the correlation was less satisfactory. Although it is not possible at present to draw definite conclusions about the real value and advantages of microhysteroscopy in the diagnosis of female infertility, we are convinced that it is of great use and that it should be at the basis of any investigation involving the infertile woman.     

Computed tomography and tumor markers as diagnostic alternatives to second-look surgery in the treatment of malignant ovarian tumors]

Advanced malignant ovarian cancers are treated, after initial surgery, with first-choice mono/polychemotherapy, the response to which is evaluated by means of second-look laparotomy. The poor prognostic value of second-look results, the incidence of false negatives, the lack of valuable second-choice therapies, and the high incidence of complications after repeated interventions, lead to the testing of diagnostic imaging modalities--especially CT and tumor markers (Ca 125 and Ca 15-3). To define their actual clinical value, CT and serum assays of Ca 125 and Ca 15-3 have been performed on 32 treated patients affected with ovarian cancers (stages II-IV), who were clinically free of disease. The results have been compared with second-look pathology, but especially with patient follow-up (min. 24 months). Second-look laparotomy yielded a high number of false negatives (9/22 = 41%); moreover, many important/severe complications were observed. Thus, its value appears to be questionable. CT exhibited high positive predictive value (76.9% over the 24-month follow-up); high for both Ca 125 and Ca 15-3 (100% respectively, at 24-month follow-up) thus, few false positives were observed. Moreover CT, having higher sensitivity (55.5%) than Ca 125 (11.5%) and Ca 15-3 (27.7%), has greater diagnostic capabilities, especially when the lesion is in extraperitoneal location.     

Spatial and temporal pattern of purkinje cell degeneration in shaker mutant rats with hereditary cerebellar ataxia

Temporal-spatial patterns of surviving Purkinje cells were studied quantitatively in a rat mutant (shaker) with differential hereditary cerebellar ataxia and Purkinje cell degeneration. Shaker rat mutants are characterized behaviorally as mild if they are ataxic or as strong if they have ataxia and tremor. Purkinje cells degenerate in both mild and strong shaker mutants, but the temporal and spatial patterns of cell death are strikingly different. In mild shaker mutants, Purkinje cell death is temporally restricted, with 31-46% of the Purkinje cells in lobules I-IX dying by 3 months of age. Very few Purkinje cells degenerate after this age. Purkinje cell death is spatially random. In lobules I-IX, every second, third, or fourth Purkinje cell degenerates. Purkinje cells in lobule X do not degenerate. In strong shaker mutants, Purkinje cell degeneration is temporally protracted and spatially restricted. By 3 months of age, most Purkinje cells in lobules I-VIa, -b, and -d, and -d have degenerated. Numerous Purkinje cells in the paravermis of lobules VIIb-VIII have also degenerated. Surviving Purkinje cells in the vermis and lateral hemisphere of lobules VIIb-VIII are aligned in parasagittally oriented stripes or transversely oriented bands. Purkinje cells continue to degenerate in localized areas of the posterior lobe such that, by 18 months of age, surviving Purkinje cells are limited primarily to lobules VIc, VIIa, IXd, and X. Quantitative analysis indicates that none of the Purkinje cells in these lobules degenerate.     

Risk factors for endometrioid, mucinous and serous benign ovarian cysts

To evaluate the risk factors for serous, mucinous and endometrioid ovarian cysts, data were collected in a case-control study conducted in the greater Milan area based on 202 women with benign cysts (114 endometrioid and 88 serous or mucinous) of the ovary and 1127 controls. Questions were asked about menstrual and reproductive characteristics, marital status, education, history of various diseases, and lifetime use of oral contraceptives and other hormonal treatments. Higher social class, earlier menarche and longer interval between age at first marriage and first birth, a likely indicator of subfertility, were associated with an increased risk of serous, mucinous and endometrioid cysts. Women with endometrioid cyst were characterized by low parity, less frequent irregular or long menses, more frequent oral contraceptive use and low body mass index, while the most relevant risk factor associated with serous and mucinous cysts was greater age at first birth. The present data point out the epidemiological differences between endometrioid and serous or mucinous cysts. Further, they suggest that analyses of risk factors for epithelial ovarian cancer subdivided by various histotypes may be of interest in order to confirm possible heterogeneities in the aetiology of ovarian epithelial neoplasms.