Muscular hypertrophy after chronic radiculopathy.

In four patients, calf muscular hypertrophy developed after the onset of sciatica. Hypertrophic muscles were weak and showed electromyographic signs of denervation. In all cases, calf muscle biopsy showed striking hypertrophy of type 1 and, especially, type 2 muscle fibers. This hypertrophy was associated with other signs indicating a neurogenic lesion. Muscle hypertrophy is a rare finding in neurogenic lesions. Stretch and exercise of muscle are probably the causative factors.

MELAS syndrome: characteristic migrainous and epileptic features and maternal transmission.

Severe prolonged migrainous symptoms and prolonged partial status epilepticus are characteristic features of the MELAS syndrome (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes). Maternal transmission previously found in myoclonus epilepsy and ragged-red fibers (MERRF), another mitochondrial disease, is suggested in this disorder as well.

Aging of the human synovium: an in vivo and ex vivo morphological study.

Age-associated changes of the human synovium have been investigated by microarthroscopy, optical and electron microscopy, immunohistochemistry, and cytochemistry. The knee joints of nineteen 15- to 56-year-old subjects, classified as normal by inspection, were carefully examined by microarthroscopy; small synovial tissue biopsy specimens from both the suprapatellar pouch and the medial tibiofemoral gutter were taken. Microarthroscopy showed that the villi were more numerous and the vascular network and cell distribution and profiles less regular in aged individuals. These data were confirmed by scanning electron microscopy, which also showed large areas of the synovial surface devoid of cells and collagen bundles in contact with the joint cavity in aged subjects. Light and transmission electron microscopy confirmed these data and allowed evaluation of the number, distribution, shape, and internal organization of cells as well as the distribution of vessels and the organization of the extracellular matrix in the full thickness of the synovium (down to 2 mm). Particular attention was paid to synovial lining cells, among which three main phenotypes could be recognized: synthetic type (present at all ages and hypertrophied in aged subjects), macrophagelike (increasing with age), and fibroblastlike. Collagen increased with age. Further studies are needed for comprehensive understanding of age-associated changes in the human synovium.

Neurosecretory-like granules in non-Hodgkin's malignant lymphomas.

A case of high-grade non-Hodgkin's malignant lymphoma with an immunologically proven B-cell origin is reported; 20 to 30 per cent of the neoplastic cells displayed electron-dense neurosecretory-like granules at the ultrastructural level. This observation confirms the existence of such a finding in lymphomatous growths and stresses its irrelevance in the differential diagnosis between non-Hodgkin's malignant lymphomas and apudomas.

Giant cell tumor of major salivary glands: report of three cases, one occurring in association with a malignant mixed tumor.

Three cases of a heterofore undescribed neoplasm of major salivary glands morphologically similar to giant cell tumor of bone are presented. All tumors were located in the parotid gland of adult individuals, and all patients are alive and well following surgical excision. One of the three cases was associated intimately with a malignant mixed tumor (carcinoma in pleomorphic adenoma). Ultrastructural and immunohistochemical studies failed to provide conclusive evidence about the specific nature of the tumor cells. The major salivary glands should be added to the long list of organs in which extraskeletal giant cell tumors have been observed, whether alone or in association with an epithelial malignancy.

An animal model based on the Sprague Dawley rat for the evaluation of ototoxicity.

Various methodological approaches that can be used to detect ototoxic effects caused by the administration of various substances are presented, using the Sprague-Dawley rat as an animal model. Electrophysiological data are also presented to show how the model behaves with potentially ototoxic (hyaluronic acid) and initially inert (hydroxy-propyl-methyl-cellulose) substances.

A 48-hour preservation of an isolated human uterus: endometrial responses to sex steroids.

Human uteri were perfused with Krebs-Ringer bicarbonate-glucose buffer with and without estrogens and progesterone for a period of up to 48 hours to preserve a viable organ, which was responsive to hormones. Flow rates of 12 to 35 ml/minute per artery were fully distributed into the organ, with pressure values ranging from 80 to 120 mm Hg. Arteriovenous gradients of oxygen and carbon dioxide tensions as well as the levels of lactate, lactic dehydrogenase, and creatine kinase released in the perfusate, indicators of tissue ischemia or cell necrosis, showed a good preservation of the organ for up to 48 hours. The light- and electron-microscopic examinations of endometrial and myometrial tissues taken before and during perfusion confirmed this result. The extracorporeal perfusion of uteri with buffer containing estrogens plus progesterone exhibited secretive modifications of the proliferative endometrium, thus suggesting the viability of the organ and its responsiveness to sex steroids.

Intra-articular hyaluronic acid in the treatment of osteoarthritis of the knee: clinical and morphological study.

OBJECTIVE: To evaluate, in a pilot, open clinical trial on 40 patients with knee osteoarthritis, the structural changes in the synovial membrane and cartilage following treatment with intra-articular hyaluronic acid (HA-Hyalgan). METHODS: The structural effects of HA given as 5 weekly injections (20 mg/2 ml once a week for 5 weeks), were evaluated by microarthroscopy and morphological analysis of biopsy samples taken at baseline and after 6 months, under blind conditions. Clinical efficacy was also evaluated using visual analogue scales for pain and functional parameters. RESULTS: At 6 months, the microarthroscopic evaluation indicated that the majority of the patients (60%) showed no changes compared to baseline, while 32.5% of the patients showed improvement in the grading and/or extension of cartilage lesions and 7.5% showed a worsened condition. These changes were accompanied by a statistically significant reduction in the synovial inflammation (p = 0.001). The results were confirmed by morphological examination of the cartilage and synovial membrane. At 6 months compared to baseline, a statistically significant reconstitution of the superficial amorphous layer of the cartilage (p = 0.0039), an improvement in the chondrocyte density (p = 0.0023) and vitality (p = 0.05), and a statistically significant reduction in synovial inflammation (p = 0.0001) accompanied by a significant increase in the synovial repair process (p = 0.0001) were observed. Significant and long lasting improvement in pain and joint mobility were also seen after HA treatment. Joint effusion, when present, was reduced. The treatment was well tolerated. CONCLUSION: Hyalgan represents a useful therapy for knee OA, with long-lasting symptomatic efficacy and potential positive effects on joint tissues. Other studies, in particular placebo-controlled studies, are warranted to confirm these promising results observed on joint tissues.

Microvascular changes in progressive systemic sclerosis: immunohistochemical and ultrastructural study.

Fifteen patients affected by Progressive Systemic Sclerosis have been studied. With immunofluorescence, specific antibodies against collagen type IV and laminin clearly outlined the microvessels, while endothelial cells showed a brilliant heavy fluorescence for vimentin antibodies. In the deep dermis, fibronectin proved to have increased. At electron microscopy, microvessels appeared with occluded lumina due to the presence of swollen endothelial cells. Endothelial cytoplasm was filled with intermediate filaments (vimentin type), generally condensed into peripherally located bundles or in perinuclear rings. The perivascular basal lamina was thickened and laminated. Although these changes do not demonstrate a specific pattern, representing a common step in several connective tissue disorders, the data tend to confirm a clear involvement of the microvasculature in Progressive Systemic Sclerosis.

Mitochondrial paracrystalline inclusions in the peroneus brevis muscle of patients with peripheral neuropathy.

In a series of 50 consecutive biopsies of peroneus brevis muscle (PBm) taken from patients with ascertained or suspected polyneuropathy in the course of sural nerve biopsy, we found a high incidence (26%) of intramitochondrial paracrystalline inclusions (MPI). Five out of these 13 patients were also submitted to an additional biopsy of a proximal muscle, which in no case confirmed the finding of MPI. Six out of the 13 patients with MPI were affected by diseases with a presumably important ischemic component. The mean age of patients with MPI was quite elevated (60.7), and the difference in distribution of age between patients with and without MPI was statistically significant. No significant difference in histochemical changes was found between the group of MPI patients and a control group of age-matched patients without MPI, thus excluding that MPI in the PBm are specifically associated with other neurogenic or myopathic aspects. We conclude that aging and, probably, ischemia are largely responsible for the frequent presence of MPI in the PBm. In addition, factors intrinsic to the muscle itself, possibly related to morphological, physiological, or biochemical peculiarities, may also influence the development of MPI.

Familial amyloid polyneuropathy: report of a family.

We report an Italian family affected by familial amyloid polyneuropathy. In two siblings, the diagnosis was confirmed by skin biopsy which revealed an unusual involvement of cutaneous nerves. Immunohistochemical studies confirmed the presence of prealbumin in the amyloid deposits.

Skeletal muscle and peripheral nerve changes caused by chronic arterial insufficiency--significance and clinical correlations--histological, histochemical and ultrastructural study.

A histological, histochemical and ultrastructural study on muscle changes in chronic arterial insufficiency has been carried out in 40 patients. Muscle biopsy probes were taken in each patient either from the gastrocnemius or rectus femoris. In 7 patients submitted for amputation of a lower limb due to a more severe vascular disease, specimens were also obtained from both the sciatic and sural nerve for light and electron microscopic study. Our findings confirm the previous histological, histochemical and ultrastructural data on chronic ischemia of the skeletal muscle, suggesting that muscle damage is mainly based on a neurogenic noxa initiated by an ischemic peripheral neuropathy. In addition, many morphologic features also show the presence of a primary myopathic noxa, possibly depending on the direct damage of the mitochondrial respiratory chain by the deficit of the muscle blood supply.

Abnormal muscle mitochondria in ischemic claudication.

The gastrocnemius and quadriceps muscles findings in 18 patients with chronic arterial insufficiency were reviewed with regard to mitochondrial changes. Prominent mitochondrial alterations were present in eight out of 18 patients. The comparison of clinical data between patients with and without mitochondrial changes revealed that in this latter group all patients were at stage IV, whereas the degree of ischemic disease was milder in the other group: the difference in distribution of patients at stage IV between the two groups was statistically significant. This supports the view that mitochondrial changes are expression of adaptive modification rather than damage.

Primary osteosarcoma of the uterine corpus. Report of a case and critical review of the literature.

Uterine osteosarcoma represents an extremely rare pure heterologous sarcoma of the uterus. In the present case osteosarcoma occurred primarily in the uterine cavity of a 56-year-old woman. The tumor was anaplastic and the presence of different proliferative patterns caused differential diagnostic problems with various malignant tumor types. The osteoid features of extracellular matrix were demonstrated by electron microscopy. Clinical and pathological features of previously reported cases of uterine osteosarcoma are critically reviewed.

Report of a case of non-Hodgkin's lymphoma of large multilobated cell type with B-cell origin.

Large multilobated nuclei lymphoma is a rare entity that is characterized morphologically by large neoplastic elements with prominent nuclear lobations and clinically by a predilection for extranodal sites and a favorable prognosis. According to the data collected to date, the neoplasia is thought to be of T-cell origin. The authors describe the clinical, morphologic and immunohistochemical findings of a case of non-Hodgkin's lymphoma with large multilobated nuclei that showed a definite B-lymphocyte origin.

Mammary carcinoma with argyrophilic cells: an immunohistochemical and ultrastructural study.

The immunohistochemical and ultrastructural findings of 7 primary argyrophilic tumors of the breast are described. Five cases were selected because of a growth pattern reminiscent of a "carcinoid" tumor and 2 were obtained from 70 consecutive common carcinomas. All patients were females (mean age 68.8) and none had clinical evidence of hormonal secretion. On ultrastructural examination dense-core granules were seen in addition to findings more suggestive of a common carcinoma. Immunoperoxidase stainings for ACTH, calcitonin etc. were negative in all tumors. The authors believe that organoid growth pattern, argyrophilia and dense-core neurosecretory-like granules are not sufficient elements to demonstrate the endocrine nature of a breast neoplasm.

Comparative ototoxic potential of hyaluronic acid and methylcellulose.

In experimental animal studies, exogenous hyaluronan (HA) has been shown to exert beneficial effects on the healing of tympanic membrane perforation. As any other exogenous substance, HA may prove potentially toxic, by filling the middle ear cavity, to the sensory cells of the organ of Corti. Electrophysiological (ABR) and morphological studies were carried out in the rat to examine the auditory function and the structure of the sensory epithelium. Rats received either HA or hydroxy-propyl-methyl-cellulose by trans-tympanic injection (middle ear cavity was completely filled up) and were compared to untreated, age- and weight-matched rats. In both treated groups ABR revealed transitory, mild conduction hearing loss, in particular for high frequencies, until day 7 postinjection. This loss recovered completely within the 15th day. Morphologically, no significant degenerative/necrotic lesions were observed in the organ of Corti, from both treated groups.

[Spontaneous reparation of post-traumatic tympanic perforation: an experimental study in rats]. / Riparazione spontanea della perforazione timpanica post-traumatica: studio sperimentale nel ratto.

In most patients tympanic membrane perforation spontaneously repairs itself. Nonetheless, in several cases the perforation persists due either to traumatic or phlogistic damage. Although the membrane perforation healing process has been under study for over a century there are still two contrasting theories. One of these theories asserts that repair takes place through the growth of granulation tissue while the other believes that epithelial migration is at the basis of healing. In the present study an experimental animal model (rat) was used in order to assess the staging of the natural evolution of post-traumatic membrane perforation and to characterize, from a morphological and sub-microscopic point of view, the cellular population and microstructural aspects of the extracellular matrix. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) were employed to evaluate the progress in tympanic membrane healing and to make a comparison with the most recent theories. Eighteen Sprague-Dawley rats weighing 230-260 gr of the same age (10 weeks) were used in the study. The animals were anesthetized by intraperitoneal injections of Na-pentobarbital (NembutalR) (45 mg/Kg) and, under operating microscope, bilateral perforation of the upper rear quadrant of the pars tensa was performed with a myringotomy lancet. The animals were subjected to periodic follow-ups over next 30 days. Three animals were sacrificed during each control and the tympanic membrane was removed for TEM and SEM study. On the basis of the present study the following conclusions can be drawn: a) primary healing of the lesion is through granulation tissue; b) the healed T.M. is composed of three normal layers as is the normal T.M.; c) the presence of fibroblasts in the intermediate neoformed fibrous layer leads one to conclude that its extracellular matrix is produced and organized "in situ"; d) the neoformed lamina propria has a disorganized, fibrous structure.