Halting hyaluronidase activity with hyaluronan-based nanohydrogels: development of versatile injectable formulations.

Hyaluronan (HA) is among the most used biopolymers for viscosupplementation and dermocosmetics. However, the current injectable HA-based formulations present relevant limitations: I) unmodified HA is quickly degraded by endogenous hyaluronidases (HAase), resulting in short lasting properties; II) cross-linked HA, although shows enhanced stability against HAase, often contains toxic chemical cross-linkers. As such, herein, we present biocompatible self-assembled hyaluronan-cholesterol nanohydrogels (HA-CH NHs) able to bind to HAase and inhibit the enzyme activity in vitro, more efficiently than currently marketed HA-based cross-linked formulations (e.g. Jonexa™). HA-CH NHs inhibit HAase through a mixed mechanism, by which NHs bind to HAase with an affinity constant 7-fold higher than that of native HA. Similar NHs, based on gellan-CH, evidenced no binding to HAase, neither inhibition of the enzyme activity, suggesting this effect might be due to the specific binding of HA-CH to the active site of the enzyme. Therefore, HA-CH NHs were engineered into injectable hybrid HA mixtures or physical hydrogels, able to halt the enzymatic degradation of HA.

Glycosylated forms of nuclear lamins.

Chromatin and pore complex-lamina preparations were obtained from pig and chicken tissues, and their proteins were analysed by mono- and bidimensional electrophoresis. A glycosylated form of lamin A, recognized by concanavalin A, was shown to be present in at least 3 of the tissues examined. Glycosylation is suggested to be a further postsynthetic modification, besides phosphorylation and methylation, which can modify the properties of lamins.

Glycosylation of RNA polymerase II from wheat germ.

RNA polymerase II from wheat germ was analyzed for the presence of sugars. The two largest subunits and the 27 and 25 kDa subunits were found to be glycosylated by a variety of sugars. However, no N-acetylglucosamine was detected, which was found by Kelly et al. (J. Biol. Chem. (1993) 268, 10416-10424) in the largest subunit of RNA polymerase II from calf thymus. Thus it appears that the regulatory function of this sugar, postulated by Kelly et al., is performed in the wheat germ enzyme by other monosaccharides. Carbohydrate analysis of the two largest subunits of the calf thymus enzyme also revealed the presence, beside N-acetylglucosamine, of other sugars. Some similarities in the features of glycosylation of the two polymerases, isolated from very different organisms, suggest that the sugar moieties have an important role in the structure and/or function of these enzymes.

DNA-nuclear matrix interactions analyzed by cross-linking reactions in intact nuclei from avian liver.

To detect the interactions of DNA with the nuclear matrix proteins, DNA-protein cross-linkages were induced in intact nuclei from chicken liver by the use of cis-diammine dichloroplatinum. Methods have been devised for fast purification both of the proteins and of the DNA fragments involved in the cross-linked complexes. By Southern-Western blotting a number of matrix proteins isolated from the complexes have been shown to recognize specifically DNA sequences present in the cross-linked DNA fragments. This experimental approach not only allows to identify the nuclear matrix-DNA interactions existing in the nucleus before its disruption, but also provides a preparation of matrix proteins enriched in those species which are involved in such interactions and which can therefore be detected with high sensitivity.

Birthday of peripheral nervous system surgery: the contribution of Gabriele Ferrara (1543-1627).

SURGERY OF THE peripheral nerves has only recently achieved brilliant results thanks to technological advances in the development of neurosurgical instrumentation. In past centuries, few surgeons made relevant contributions to this topic and improvement was slow and difficult. Avicenna, Guglielmo da Saliceto, and Guido Lanfranchi reported some attempts to suture nerves directly, but Gabriele Ferrara was the first to give a lucid and succinct description of suturing of the stumps of a transected nerve. He described applying gentle traction on the retracted stumps, suturing using a special needle with an eye, after immersion in a decoction of red wine, rosemary, and roses (alcoholic disinfection?), and, finally, insulating the sutured segment with a mixture of oils. We are celebrating the 400th anniversary of the first edition of his fundamental work (1596-1996), and we truly esteem this surgeon, a pioneer of peripheral nerve surgery wo primarily contributed to its progress.

Association between neuroepithelial tumor and multiple intestinal polyposis (Turcot's syndrome): report of a case and critical analysis of the literature.

We report a case of association of a brain tumor with multiple intestinal polyposis (Turcot's syndrome) and offer a critical analysis of the relevant literature with a view to revising the classification of the syndrome in relation to familial multiple polyposis and Gardner's syndrome. For this purpose, we considered only cases of intestinal polyposis associated with a primary neuroepithelial tumor (medulloblastoma, glioma, or glioblastoma) as originally described by Turcot. Differences emerged, depending on the central nervous system tumor type, which suggests that this neoplastic association may be classified as two distinct syndromes.

Long-term prognosis for atypical and malignant meningiomas: a study of 71 surgical cases.

To contribute to a better understanding of the prognostic differences between atypical and malignant meningiomas as defined by the World Health Organization (WHO) and the influence of the grade of initial surgical excision on postoperative course, 42 cases of atypical and 29 of malignant meningioma were studied, along with long-term follow up. The two groups were compared with respect to long-term survival, recurrence-free survival, and median time to recurrence. The prognostic significance of the Simpson grade of surgical resection and tumor location was also considered. Survival at 5 and 10 years was recorded in 95% and 79%, respectively, of patients with atypical meningioma and in 64.3% and 34.5% of patients with malignant meningioma (p = 0.001). Recurrence-free survival and median time to recurrence were also significantly longer in patients with atypical than in those with malignant meningiomas: 11.9 versus 2 years (p = 0.001) and 5 versus 2 years (p < 0.0041), respectively. Six (26%) of the 23 recurring atypical meningiomas became malignant. Simpson Grade I resection and location in the cerebral convexity, which were closely related, were found to be associated with a significantly better clinical course in the entire series (p < or = 0.0016). Patients with atypical meningiomas fared better than those with malignant meningiomas after incomplete surgical excision (Simpson Grades II-III), but the difference was not statistically significant. Multivariate analysis using the Cox model indicated that radical extirpation (Simpson Grade I vs. II-III) and histological findings (atypical meningioma vs. malignant meningioma) were significantly related to prolonged survival (p < 0.0003 and p < 0.0388, respectively). In conclusion, the current study shows that for most patients with atypical meningioma the prognosis was less severe than for those with malignant meningioma, but the risk of a downhill course resulting from malignancy after incomplete resection and recurrence was not negligible (26%). In addition, the WHO classification was found to be inadequate for a minority of the atypical meningioma cases, which currently have the same unfavorable course as cases of malignant meningioma. The results also indicate that objective Simpson Grade I extirpation of convexity meningiomas can be successful despite histological findings of malignancy.

Recurrence of spinal ependymoma. Risk factors and long-term survival.

STUDY DESIGN: A study was conducted on 78 patients with spinal ependymoma. The authors divided the patients in two groups. OBJECTIVES: The aim was to elicit the risk factors for recurrence and the fate of patients who underwent second operations. SUMMARY OF BACKGROUND DATA: Group A is made up of 59 patients with no signs of recurrence at follow-up (median 14 years), and group B is made up of 19 patients who had undergone second operations because of relapses (follow-up median 12 years). METHODS: The clinical and therapeutic characteristics and survival of the two groups were compared statistically. RESULT: Analysis of the series shows that the most important points in predicting recurrence are length of clinical history (P < 0.05), gross appearance of the tumor at first operation (P < 0.05), and type of excision (P < 0.001). CONCLUSION: These factors proved to be closely interrelated. In the event of recurrence, spinal ependymoma has an adverse prognosis.

Medulloblastoma in late adults. Case report and critical review of the literature.

BACKGROUND: Medulloblastoma in late adults (older than 65 years) is an exceptional occurrence; in fact only 8 cases are reported with complete clinical notes in the literature. METHODS: The authors describe a case of medulloblastoma occurring in a 68-year-old man and analyzed cases reported in the literature. RESULTS: The overall average age of the patients was 72.8 years (range 67-88 years), and the male prevalence of this tumour (70% of cases) seems to be unrelated to age. There is a lateral predominance in late adults (77.7% of cases). Seven patients underwent operation and subsequently these patients underwent a course of radiation therapy. Only two patient was treated with postoperative chemotherapy. Median survival for seven patients treated was 43.2 months (range 23-96 months). CONCLUSIONS: It is interesting to note that: 1) histological analysis revealed a classic type medulloblastoma (88.8% of cases) similar to the children: 2) site of the tumor is lateral similar to the adults (77.7% of cases).

Cerebellar mutism after posterior cranial fossa surgery.

Mutism is a rare sequel of PCF tumor removal. Three patients aged 5 to 20 years old with mutism after posterior fossa surgery are presented. Suboccipital craniectomy was performed in all patients with grossly total removal of a medulloblastoma. The mutism that may occur after an operation for a PCF lesion has been explained in functional and/or organic terms. To date, 24 similar cases of mutism following cerebellar operations have been reported in the literature. We review the features of the syndrome in the light of the published cases and speculate on the underlying physiopathology. The absence of long tract or other brain stem signs, together with a presence of dysarthria during the recovery of speech, suggested a organic cerebellar cause of the mutism.

Late solitary cerebral metastasis from renal carcinoma.

The authors describe 2 patients with solitary cerebral metastasis occurring 13 years after treatment for a renal tumor in one and 17 in the other. Both patients are alive 30 and 36 months after surgery respectively. The pathogenetic and therapeutic features typical of this type of solitary metastasis with late-onset are discussed.

Radiation-induced osteosarcomas of the skull: report of two cases and review of the literature.

Osteosarcoma of the skull as a second neoplasm after radiation therapy is unusual. This neoplasm generally occurs after doses of over 10 Gy. CT, MRI and biopsy are the main diagnostic procedures for this lesion. We report two other cases of osteosarcomas of the skull and review the pertinent literature.

Intracerebral schwannoma. Case report.

A case of intraparenchymal schwannoma is presented. A 61-year-old woman, with stigmata of von Recklinghausen's neurofibromatosis (NF-2), presented with a history of weakness of the right lower limb for 2 months. She was investigated by MR which showed a circular mass with a maximum diameter of 5 cm in the right parieto-occipital lobe. The tumor was removed in toto via a left parieto-occipital craniotomy. The patient was discharged two weeks after the operation and remains well now 2 years later. The clinical and neuroradiological findings of reported intraparenchymal schwannomas, including the case reported here, are discussed.

Spinal ependymomas and papilledema: report of 4 cases and review of the literature.

We report 4 cases of ependymoma of the filum terminale with associated intracranial hypertension syndrome. After analyzing the relevant published work, we consider the possible pathogenetic hypotheses for this rare association.

Intradural tumors of the cauda equina: a single institution review of clinical characteristics.

A retrospective review of 106 cases of intradural tumors of the cauda equina are presented, subdivided into 5 groups according to their histological characteristics. For each group the clinical course and long-term postoperative results were analyzed: it emerged that differential diagnosis between neurinomas, meningiomas or non-tumoral lesions is not possible based on clinical findings alone and that neuroradiological diagnosis is more accurate when MRI is employed. Long-term prognosis was always favorable with the exception of the group of ependymomas. Nevertheless, early diagnosis in the latter group of tumors gives excellent results because prognosis is apparently directly correlated to the length of preoperative clinical history.

Prognostic factors in intramedullary astrocytomas.

This report presents a retrospective prognostic study of 65 patients with intramedullary astrocytoma surgically treated between 1953 and 1990. Median survival and statistical survival at 5 years were assessed in relation to clinical, histological and therapeutic factors for each patient. Results showed that factors positively influencing the prognosis are low histological grade of the tumour and good pre- and post-operative general conditions. Among the grade II astrocytomas, the fibrillary and protoplasmatic types presented longer survival times regardless of the type of removal performed. In anaplastic astrocytomas the simultaneous presence of certain morphological features indicative of higher malignancy negatively influenced survival. The degree of resection did not influence average survival within each histological grade.

Occult dysraphism in adulthood. A series of 24 cases.

The results of a retrospective study of 24 adult patients with occult dysraphism are described. There were 15 males and 9 females, with an average age of 31.1 years. Specific circumstances precipitated symptomatic onset in 67% of patients. Pain, often referred to the anorectal region, was the most common presenting symptom. Bladder and bowel dysfunction were also common findings. The most common tethering lesions were intradural lipoma and a short thickened filum terminale. Myelography revealed the diagnosis of tethered conus in most cases, but the addition of CT and MRI images provided valuable structural details. The surgical outcome was gratifying in relation to pain and sensory-motor deficits but disappointing in the resolution of sphincter disorders. Our conclusion is that symptoms and/or signs of TCS with onset in adult life are not invariably irreversible.

Solitary cerebral metastasis from melanoma: value of the 'en bloc' resection.

The authors report 19 cases of solitary cerebral metastases from malignant melanoma. In 15 patients, the primary lesion was known at the time the metastasis was diagnosed; deltoid-scapular in 4 cases, thoracic in 5, inguinal in 4 and neck in 2. The primary location was unknown in 4 patients. Presenting symptoms were: epileptic seizures in 9 cases, headache in 8, strength deficit of the limbs in 2. In 3 patients (16%) neurological symptoms were the first clinical sign of the systemic tumor; in 16 cases (84%) there was a long interval between treatment of the primary and appearance of the cerebral metastasis (average 3.8 years; median 3.4 years). All patients were submitted to surgery and radiotherapy (whole-brain in 14 and radiosurgery in 5). In 10 cases the lesion was removed 'en bloc' (no internal touch technique). Average survival was 9 months (median 8 months) and was influenced by 'en bloc' resection and whole-brain irradiation. None of the patients operated by the 'no touch technique' presented a recurrence.

Solitary plasmacytoma of the skull: report of two cases.

We report two cases of solitary plasmacytoma of the skull, a very unusual presentation and location of this tumor. There seems to be no difference in prognosis between the tumor originating from the skull (osseous form) and from the dura mater (non-osseous form), differently from the data of other parts of the body. The risk of secondary multiple myeloma appears to be low but the mean follow-up is too short for any conclusion on this point.

Extradural haematoma of posterior cranial fossa.

Two cases of extradural haematoma of posterior fossa with an acute course are reported. After trauma, the two patients did not show any symptom for a time of 16 and 18 hours respectively. Both of them showed a status of coma at the moment of hospitalization. The haematoma was diagnosed by CT scan. Both of them were immediately operated in order to evacuate the haematoma. Afterwards, one of the patients presented cerebellar symptoms while the other did not show any neurologic deficiency. The authors have analysed cases of this rare form of post-traumatic pathology referred in the literature since 1941, examining them from a clinical, therapeutic and prognostic point of view. The best diagnostic and therapeutic procedures to follow on this subject are then stressed.