Treatment of large complex cranial bone defects by using hydroxyapatite ceramic implants

Hydroxyapatite ceramic implants were used in the reconstruction of very large and complex-form cranial bone defects in nine patients. The bone defects were the result of craniectomy after infections and other complications such as severe brain edema, after neurosurgery, and as a result of trauma, subdural hemorrhage, and surgery for brain tumor. The size, shape, and curvature of the hydroxyapatite ceramic implants were determined based on high-precision, full-scale models fabricated through a laser lithographic molding method by using computed tomographic data. The use of this method allowed the fabrication of hydroxyapatite ceramic implants of shapes that accurately matched the area of bone defect, allowing for a minimum of adjustment during the operation even with a complex-form implantation. Not only were good cranial contour reconstructed and aesthetically satisfactory results obtained in the cases treated by incorporating this series of techniques, but neurologic conditions present in some cases were also improved to some extent. The postoperative course has been steady for all nine patients, with no blood transfusions required during or after the operations and no implants requiring removal because of infection or other postoperative complications. The average length of postoperative hospitalization for the nine cases was 11.7 days, remarkably short considering the clinical conditions.     

Use of the united suture in microvascular anastomoses.

A technique for microvascular anastomoses is described. It leaves one suture united until the last, a maneuver which helps to avoid picking up the posterior wall with the anterior wall.     

Late effects of ionizing radiation on the microvascular networks in normal tissue

Damage to the microvascular networks constitutes one of the most important components of ionizing radiation damage to normal tissue. Previously, we have reported the early (3, 7 and 30 days postirradiation) effects of ionizing radiation on the structure and function of normal tissue microvascular networks. Here we report on the late effects of ionizing radiation on the structural and functional changes in microvascular networks in locally irradiated (single 10-Gy dose) hamster cremaster muscles observed 60, 120 and 180 days postirradiation; age-matched animals were used as controls. As in the previous study, intravital microscopy was used to measure structural and functional parameters in complete microvascular networks in vivo. A factorial design was used to examine the effects of radiation status, time postirradiation, and network vessel type on the structure and function of microvascular networks. Our results indicate that the progression of radiation-induced microvascular damage continues during the late times but that there is partial recovery from radiation damage within 6 months postirradiation. Red blood cell flux, red blood cell velocity, and capillary blood flow in irradiated networks at 180 days postirradiation were significantly greater than control levels. As at the early times, all vessel types were not damaged equally by radiation at every time.     

Early effects of ionizing radiation on the microvascular networks in normal tissue

Microvascular networks, which control the delivery of oxygen and nutrients and the removal of metabolic waste, are the most sensitive part of the vascular system to ionizing radiation. Structural and functional changes in microvascular networks were studied in locally irradiated (single 10-Gy dose) hamster cremaster muscles observed 3, 7 and 30 days post-irradiation. Networks were selected in reference to a well-defined location in the tissue to reduce heterogeneity due to spatial variations. Intravital microscopy was used to measure structural and functional parameters in vivo. A factorial design was used to examine the effects of radiation status, time postirradiation, and network vessel type on the structure and function of microvascular networks. While the diameter of microvessels in control animals increased significantly with age, vessel diameter in irradiated vessels decreased significantly with age. Red blood cell velocity in irradiated networks at 3 and 30 days postirradiation was significantly lower than in control networks. There was a significant decrease in capillary surface area and a significant increase in vessel hematocrit in irradiated animals. Blood flow in irradiated vessels was significantly lower than in control vessels. Changes in functional parameters were evident at 3 days postirradiation while changes in structural parameters occurred later. All vessel types were not damaged equally by radiation at every time examined.     

Reconstruction of an extreme frontal and frontobasal defect by microvascular tissue transfer and a prefabricated titanium implant

A 30-year-old man was referred to us with an extreme frontal and frontobasal defect from a motorbike accident 12 years before. Multiple attempts at frontal and frontobasal revision and reconstruction had been performed over the years, with several episodes of meningitis. Reconstruction was planned in two steps. First, a revision of the anterior skull base with mobilization of meningeal adhesions and duraplasty, removal of infected masses of polymethylmethacrylate out of the upper ethmoid sinuses, and coverage with a deepithelialized latissimus dorsi free flap were performed. In the second step 3 months later, aesthetic forehead reconstruction was achieved with a pre-fabricated individual titanium implant. The predictable result of this two-step reconstruction was very pleasing. Safe separation of the cranial cavity from the upper airways was essential, requiring free tissue transfer in this case, and is a prerequisite for any alloplastic forehead reconstruction. Timing of the two-step procedure, including the CT data acquisition; handling of soft tissues, bone, and foreign material; and construction details of the implant demonstrate the necessary complex management of this, the most difficult case of the 88 applications of the new computer aided design and manufacturing technique thus far. Even the most elaborate computer aided preparation cannot be successful without consideration of established surgical principles.     

Enhanced radiation damage to the erythrocyte membrane in the presence of azide and other anions.

Radiation-induced potassium loss from erythrocytes and haemolysis were enhanced by the presence of azide at the time of exposure. The enhancement occurred with post-irradiation incubation at 37 or 4 degrees C, but was inhibited by formate or ethanol. Other anions, which produce radicals known to react selectively with only a few amino acids, gave rise to a similar but lesser enhancement. It is proposed that azide radicals are more effective in producing erythrocyte damage than the OH radicals from which they derive, and that the azide radical should be regarded as another selective secondary radical. The data can be used to infer differences in the mechanisms of damage leading to potassium loss or haemolysis.     

The relationship between the number of sutures and the strength of microvascular anastomoses.

The relative strengths of microvascular anastomoses in rat femoral arteries were measured, comparing controls (no anastomosis) to those with 4, 6, 8, 10, 12, and 14 stitches. The ones in which 8 sutures were used most closely paralleled the control state, whereas those with 4 or 6 sutures were clearly inferior. With a greater number of sutures the vessel behaves as a "shorter" vessel, with the anastomosis becoming the weakest part of the vessel.     

Reconstruction of heel and sole defects by free flaps

One latissimus dorsi musculocutaneous flap and five radial forearm flaps were used in reconstruction of weight-bearing parts of the heel and sole, the follow-up period being 7 to 38 months. Additional injuries such as forefoot amputations or amputations of the other leg were present in four patients. There was no flap loss. The latissimus dorsi flap proved to be too bulky and showed recurrent ulcerations, several reoperations were necessary, and definite healing has not occurred. The five forearm flaps gave good results, with a walking range from 2 hours to unimpeded walking. Complications included fissuring at the edges of one large flap and a local infection which was successfully treated. Cutaneous sensation returned in all but one flap, where it was reduced preoperatively due to a meningomyelocele. The results indicate that the fasciocutaneous radial forearm flap should be taken into consideration for reconstruction of weight-bearing areas of the heel and sole. Shortcomings of this flap include an unsightly donor defect and possible hair growth on the flap.     

Determination of the interface of a large protein complex by transferred cross-saturation measurements

In an earlier paper, it was shown that the cross-saturation method enables us to identify the contact residues of large protein complexes in a more rigorous manner than is possible using chemical shift perturbation and hydrogen-deuterium exchange experiments. However, there are limitations within the determination of the contact residues by the cross-saturation method, in that the method is difficult to apply to protein complexes with a molecular mass over 150 kDa and/or with weak binding, since the resonances originating from the complexes should be observed directly in the method. In the present work, to overcome these limitations, we carried out the cross-saturation measurements under conditions of a fast exchange between free and bound states on the NMR time-scale, and determined the contact residues of the complex of the B domain of protein A and intact IgG, which has a molecular mass of 164 kDa and shows weak binding.     

Reconstruction of Achilles tendon and calcaneus defects with skin-aponeurosis-bone composite free tissue from the groin region

Eight patients had reconstructive surgery for soft-tissue, associated Achilles tendon, and calcaneus defects on the posterior aspect of the ankle. In group A, those patients with skin, soft-tissue, and Achilles tendon loss were treated with free groin flaps that included sheets of the external oblique aponeurosis based on the superficial circumflex iliac vessel. The groin flap provided skin coverage, and the aponeurosis was rolled to form a tendon-like structure to replace the Achilles tendon. In group B, those patients with an additional calcaneus bone loss were treated with free iliac osteocutaneous flaps, together with the external oblique aponeurosis based on the deep circumflex iliac vessel. The iliac bone was then utilized to reconstruct the calcaneus defect. All composite free tissue transfers were successful, except in two group B patients who suffered partial skin loss. The advantages of this technique are (1) a single, one-stage procedure, (2) faster wound healing with fewer adhesions of the reconstructed Achilles tendon, and (3) good cosmesis and minimal morbidity at the donor site.     

Clathrin heavy chain is required for pinocytosis, the presence of large vacuoles, and development in Dictyostelium

To investigate the intracellular role of the clathrin heavy chain in living cells, we have used "antisense" RNA to engineer mutant Dictyostelium discoideum cells that are severely deficient in clathrin heavy chain expression. Immunoblots stained with an anti-clathrin heavy chain antiserum revealed that mutant cells contained undetectable amounts of clathrin heavy chain protein. Similarly, Northern blots showed an absence of clathrin heavy chain mRNA. Clathrin heavy chain-deficient Dictyostelium cells were viable, but exhibited growth rates twofold slower than parental cells. Whereas many morphological features of the mutant cells were normal, mutant cells lacked coated pits and coated vesicles. Clathrin-deficient cells were also missing large translucent vacuoles that serve as endosomes and contractile vacuoles. In the absence of clathrin heavy chain, mutant cells displayed three distinct functional defects: (a) impairment in endocytosis of fluid phase markers, but competence in another endocytic pathway, the phagocytosis of solid particles; (b) defects in osmoregulation; and (c) inability to complete the starvation-induced development cycle.     

Inhibition of Polo-like kinase 4 induces mitotic defects and DNA damage in diffuse large B-cell lymphoma

Polo-like kinase 4 (PLK4), a key regulator of centriole biogenesis, has recently been shown to play key roles in tumorigenesis. Blocking PLK4 expression by interference or targeted drugs exhibits attractive potential in improving the efficacy of chemotherapy. Nevertheless, the role of PLK4 in diffuse large B-cell lymphoma (DLBCL) is still undefined. In this study, we discover that PLK4 is a potential target for the treatment of DLBCL, and demonstrate the efficacy of a PLK4 inhibitor when used in combination with doxorubicin. Pharmaceutical inhibition of PLK4 with CFI-400945 inhibited DLBCL cell proliferation and induced apoptotic cell death. The anti-tumor effects were accompanied by mitotic defects, including polyploidy and cytokinesis failure. Activation of p53 and Hippo/YAP tumor suppressor signaling pathway was identified as the potential mechanisms driving CFI-400945 activity. Moreover, CFI-400945 treatment resulted in activation of DNA damage response. Combining CFI-400945 with doxorubicin markedly delayed tumor progression in DLBCL xenografts. Finally, PLK4 was increased in primary DLBCL tissues and cell lines. High levels of PLK4 expression were associated with poor survival in the patients receiving CHOP-based treatment, implicating PLK4 as a predictive biomarker of DLBCL chemosensitivity. These results provide the therapeutic potential of CFI-400945 both as monotherapy or in combination with doxorubicin for the treatment of DLBCL.Subject terms: B-cell lymphoma, Cytokinesis, DNA damage response     

Apoptosis and necrosis induced by ultraviolet radiation in the presence of autologous plasma

This paper deals with the effect of ultraviolet (UV) light (240–390 nm) at doses of 151–3020 J/m²* on the character of the death of donors’ blood lymphocytic cells (with the use of markers of apoptotic and necrotic cell death) and on the level of the CD95 receptor—a marker of apoptotic predisposition. UV irradiation has been shown to increase the expression of CD95 receptors, which is due mainly to synthesis de novo. It is revealed that over the course of the 24-h incubation of photomodified lymphocytes (at irradiation doses of 151 and 755 J/m²) without autologous blood plasma, cell death occurs by receptor-mediated apoptosis. Action of high irradiation doses (1510 and 3020 J/m²) leads to the massive necrotic death of immunocytes. The use of autologous blood plasma during the incubation of photomodified lymphocytes allows a reduction in the amount of both apoptotic and necrotic cells.