Gunshot wounds to the head in the 16th century.

DEVELOPMENT OF FIREARMS in the 16 century produced profound changes in the art of warfare and raised new problems for the physician-surgeons. Old assumptions and wrong interpretations delayed the rational approach to the head injuries inflicted by missiles. Evolution of thought and increased experience over the century ultimately led to a surgical practice that can be regarded as the best possible solution allowed by contemporary knowledge and technology.

The spinal cord and its roots according to Galen.

Galen's methodological approach to medicine anticipated modern rules. His experiments on the spinal cord contributed greatly to our knowledge of this structure by reporting the variegated pattern of neurological impairment after sectioning at different levels. His approach to injuries of the spinal roots and peripheral nerves documents both diagnostic skill and intellectual honesty.

Return to Galen.

AT THE BEGINNING of the previous century, the English editor of a minor work by Galen called for a return to that ancient scholar after centuries of neglect. The appeal did not meet with success. Galen's reputation is currently based on renown arising from tradition, rather than an awareness of his actual contributions to medical science. His methodological approach to experimental medicine seems to have fallen into obscurity, although it anticipated modern principles. This report reviews the rise and fall in popularity of Galen's medical works, in an attempt to highlight the circumstances that still prevent a full appreciation of those writings.

Immunoscintigraphic detection of the ED-B domain of fibronectin, a marker of angiogenesis, in patients with cancer.

PURPOSE: ED-B fibronectin is expressed only during angiogenic processes and in tissues undergoing growth and/or extensive remodeling. We demonstrated previously the possibility to target and selectively deliver therapeutic substances to tumor vasculature in experimental animal models using a human recombinant antibody fragment, L19, specific for the ED-B domain of fibronectin. Here we evaluate the possibility of targeting primary tumors and metastatic lesions in cancer patients through immunoscintigraphy using (123)I-labeled dimeric L19 [L19(scFv)(2)]. EXPERIMENTAL DESIGN: Twenty patients (34-79 years of age) with lung, colorectal, or brain cancer, whose tumors had been confirmed by imaging techniques and/or histologically, were admitted to the immunoscintigraphic investigation. RESULTS: The dimeric L19 antibody selectively localized in tumor lesions in aggressive types of lung cancer and colorectal cancer. Because ED-B fibronectin is expressed only during angiogenic processes and in tissues undergoing growth and/or extensive remodeling, L19(scFv)(2) is able to distinguish between quiescent and actively growing lesions. No side effects were observed. CONCLUSIONS: The ability of L19(scFv)(2) to target tumors in patients provides the foundations for new therapeutic applications, in which the L19 antibody is engineered to selectively deliver bioactive molecules to primary tumors as well as to metastases.

Differentiation between high- and low-grade astrocytoma using a human recombinant antibody to the extra domain-B of fibronectin.

Different fibronectin (FN) isoforms are generated by the alternative splicing of the primary FN transcript. We previously demonstrated that the isoform containing the extra domain B sequence of fibronectin (B-FN), a complete type-III-homology repeat, is a marker of angiogenesis that accumulates around neovasculature only during angiogenic processes. We produced a single-chain human recombinant antibody (scFv), L19, which reacts specifically with B-FN and selectively targets tumor vasculature in vivo. We used this scFv and an antibody against a pan-endothelial marker (Factor VIII) in a double-staining procedure on specimens of low- and high-grade astrocytomas to determine the percentage of B-FN-positive vessels, (denominating the resulting value angiogenic index [AI]). Compared to vascular density and proliferative activity (evaluated using antibodies to Factor VIII and Ki67, respectively), AI correlated better with tumor grade (1.6 +/- 2.6% and 92.0 +/- 8.7% of B-FN-positive vessels in low- and high-grade astrocytomas, respectively) and was a more precise diagnostic tool than either of the two conventional methods. In fact, discriminating analysis using these three parameters showed that only AI accurately classified 100% of the cases studied, compared to 64% and 89% correctly diagnosed by vascular density and of proliferating cells, respectively.

A craniocerebral infectious disease: case report on the traces of Hippocrates.

A modern case of complicated sinusitis, with osteitis of the cranium and intraorbital-intracranial empyema, closely corresponds to descriptions reported in the Hippocratic treatise Diseases II. The therapeutic measures suggested in that work can be regarded as suitable according to modern practice. An ancient physician who followed the Hippocratic doctrine probably would have been able to recognize this complicated disease and possibly save the patient.

Occurrence of a glioblastoma-associated tenascin-C isoform in cerebral cavernomas and neighboring vessels.

OBJECTIVE: Regrowth of cerebral cavernomas after apparently complete excision, de novo occurrence, and evidence of proliferation-related patterns raise the question as to their intrinsic growth potential. A particular isoform (Type III repeat c) of the glycoprotein tenascin-C (TN-C), typically associated with the vessels of anaplastic gliomas, is regarded as a marker of vascular proliferation in lesions growing within brain tissue. This study sought to ascertain whether this isoform is expressed in cerebral cavernomas to gain further insight into the growth potential of these lesions. METHODS: Sixteen cerebral cavernomas and three fragments of normal brain underwent immunohistochemical examinations via two antibody fragments obtained by phage display technology. Previous characterization demonstrated that the fragment TN-12 recognizes the epidermal growth factor-like repeat, common to all TN-C isoforms. On the contrary, the fragment TN-11 was found to be highly specific for the Type III repeat c isoform. RESULTS: Accumulation of total TN-C was found in the vascular walls and in the interspaces between the blood cavities of all examined cavernomas. When the antibody fragment TN-11 was used, staining of the subendothelial layers occurred in both the bulk of the cavernomas and vessels of the white matter surrounding the lesions, but staining was absent in the control specimens. CONCLUSION: The distribution of the Type III repeat c isoform of TN-C, a putative marker of vascular proliferation, within cerebral cavernomas is consistent with the hypothesis of a growth potential of cerebral cavernomas. Enlargement of these lesions might involve recruitment of neighboring vasculature, which is possibly dependent on environmental conditions.