RGD peptides immobilized on a mechanically deformable surface promote osteoblast differentiation.

The major objective of this work was to attach bone cells to a deformable surface for the effective transmission of force. We functionalized a silastic membrane and treated it with 3-aminopropyltriethoxysilane (APTS). A minimal RGD peptide was then covalently linked to the aminated surface. MC3T3-E1 osteoblast-like cells were cultured on the arginine-glycine-aspartic acid (RGD)-treated membrane for 3-15 days and cell attachment and proliferation was evaluated. We observed that cells were immediately bound to the membrane and proliferated. After 8 days on the material surface, osteoblasts exhibited high levels of ALP staining, indicating that the cells were undergoing maturation. Alizarin red staining and Fourier transform infrared (FTIR) analysis showed that the mineral formed by the cells was a biological apatite. The second objective was to apply a mechanical force to cells cultured on the modified silicone membrane. Dynamic equibiaxial strain, 2% magnitude, and a 0.25-Hz frequency were applied to bone cells for 2 h. Osteoblasts elicited increased phalloidin fluorescence, suggesting that there was reorganization of the cytoskeleton. Furthermore, the applied strain elicited increased expression of the alpha(v)beta3 integrin receptor. We concluded that the covalent binding of RGD peptides to a silicone membrane provides a compatible surface for the attachment and subsequent differentiation of osteoblasts. Moreover, the engineered surface transduces applied mechanical forces directly to the adherent cells via integrin receptors.     

Head and neck lymphoma in patients with the acquired immune deficiency syndrome.

A marked increase has recently been noted in the incidence of lymphoma in patients with AIDS. These lymphomas are generally high-grade, of B-cell origin, and often involve extranodal sites. Reported here are twenty patients with AIDS in whom symptoms and physical findings developed related to the head and neck region as a result of lymphoma. The tumor was observed in a variety of sites, including the nasopharynx, orbit, submandibular triangle, anterior and posterior cervical triangles, supraclavicular fossa, and the hypopharynx. Sixteen tumors were large cell nonHodgkin's B-cell lymphomas, three were small cell nonHodgkin's B-cell lymphomas, and one was Hodgkin's disease, mixed cellularity. All were treated with combination chemotherapy. A high degree of suspicion for lymphoma is required in treating any patient with AIDS who has a rapidly enlarging mass in the head and neck. If needle aspiration is nondiagnostic, excisional biopsy should be performed after a complete head and neck evaluation. Although the development of lymphoma associated with AIDS portends a grave prognosis, prompt diagnosis will allow an improved chance of remission of the lymphoma.     

Acute normovolaemic haemodilution decreases postoperative allogeneic blood transfusion after total knee replacement

We hypothesized that the success of postoperative blood conservation after acute normovolaemic haemodilution (NVHD) is influenced by the extent of intraoperative bleeding and surgical trauma, and the timing of autologous blood transfusion. As total knee replacement is associated with minimal intraoperative but extensive postoperative blood loss, this procedure is ideally suited to acute NVHD. Therefore, to test our hypothesis, 30 patients undergoing elective total knee replacement were enrolled in a prospective, randomized, controlled study. In groups NVHD-2 and NVHD-6, before induction of anaesthesia patients were bled to a target packed cell volume (PCV) of 28-30%, and in the post-anaesthesia care unit autologous blood was transfused over a 2-h period terminating after operation at 2 and 6 h, respectively. In the control group, NVHD was not performed. After operation, platelets, fibrinogen, prothrombin and partial thromboplastin time, and liver function, urea and electrolytes were measured and compared with preoperative baseline values. Significantly (P < 0.024) more allogeneic blood was transfused in the control group (21 u.) compared with either group NVHD-2 (7 u.) or group NVHD-6 (5 u.). In the control group, despite the allogeneic blood transfusion, postoperative PCV decreased until day 4 after operation. Coagulation profile, liver function and urea and electrolytes concentrations were unaffected by the method of treatment. We conclude that for total knee replacement, acute NVHD is an effective blood conservation strategy. However, there was no difference in allogeneic blood administration between the two NVHD groups. Coagulation and liver function, and urea and electrolyte concentrations were unaffected by treatment.      

Neurobehavioral effects of antihypertensive medications.

Although millions of hypertensive individuals receive chronic treatment with antihypertensive medication, the effect on the central nervous system by these drugs is poorly understood. Such treatment, while generally well tolerated, frequently produces symptoms of drowsiness, weakness, altered memory and impaired concentration. In addition to subjective evidence derived from patient reports, a large number of investigations have now been published which attempt to objectively assess the influence of antihypertensive medication on behavioral or cognitive performance. This paper summarizes and critically evaluates experimental studies of the effect of antihypertensive medication on subjects' performance of neuropsychological tasks and reviews the pharmacologic mechanisms by which these drugs may affect behavior. The literature is incomplete in its assessment of all domains of neuropsychological performance and all drug classes, and methodologic deficiencies are common. Nonetheless, the consensus of all studies and the findings of well-designed studies in particular do not identify any notable areas of performance impairment in patients receiving antihypertensive medication. Moreover, results suggest that, in certain instances, drug treatment may even enhance performance. In light of the limitations of the literature, however, an adequate understanding of the effects of antihypertensive therapy on behavioral functioning awaits completion of large, well-designed investigations including all major drug classes and thorough neurobehavioral assessments.     

Modulatory synaptic actions of an identified histaminergic neuron on the serotonergic metacerebral cell of Aplysia

Possible sources of excitatory synaptic input to the serotonergic metacerebral cell (MCC) were determined by stimulating various neurons in the cerebral ganglion. Firing of the previously identified histaminergic neuron C2 was found to produce synaptic input to the MCC. The synaptic input consists of fast excitatory-inhibitory synaptic potentials on a background of a slow EPSP. The slow EPSP appears to be monosynaptic and chemically mediated since it persists in a solution of high divalent cations; broadening of the presynaptic spike enhances the EPSP; the size of the EPSP is a function of the Mg2+ and Ca2+ concentrations of the bathing solution; and the EPSP can be mimicked by application of histamine to the MCC. The slow EPSP, in addition to firing the MCC, can increase the excitability of the cell, even under conditions in which C2 is fired at a rate too slow to produce a measurable EPSP when the MCC is at rest potential. This property appears to be due to the fact that the slow EPSP results from an apparent decrease of membrane conductance so that the size of the EPSP increases markedly as the cell is depolarized, and the EPSP appears to be highly voltage-dependent so that it is small or absent close to the rest potential of the MCC. When the MCC is voltage-clamped, application of histamine to the bath results in an inward current that disappears when the MCC is hyperpolarized. The potential at which the histamine-induced current reverses or disappears is dependent on the concentration of external potassium, suggesting that, at least in part, the slow EPSP is due to a decrease of potassium conductance. The data on C2 are consistent with its being an element of the neuronal system that mediates a state of food arousal in Aplysia.     

Clonal chromosomal abnormalities in cutaneous T-cell lymphoma

Chromosome analysis from stimulated and unstimulated lymphocytes of blood, skin, and lymph nodes demonstrated a clonal chromosomal abnormality in eight of 46 patients with cutaneous T-cell lymphoma (CTCL). Nonclonal abnormalities were found in nine other patients. Unstimulated lymph node cultures identified the highest proportion of clonal changes. Clonal changes were found most often in patients with advanced disease, and in patients who tested positive with a monoclonal antibody previously shown to detect the T-cells involved in CTCL. Analysis of the eight abnormal clones and seven others found before or since this consecutive series showed that identifiable changes involving the known sites of T-cell receptor genes on chromosomes #7 and #14 were not usually present. An association between CTCL and chromosome rearrangements of chromosome #10 is suggested both from our cases and those found in the literature. This observation is of interest because this chromosome contains the gene for the interleukin-2 receptor.     

First and Second Generation Lithotripsy in Children: Results, Comparison and Followup

During a 5-year period 32 children and adolescents 4 to 18 years old underwent 35 extracorporeal shock wave lithotripsy (ESWL^* ) treatments for 37 calculi. The unmodified Dornier HM3 lithotriptor was used in 21 cases (60 percent) while the remaining cases were treated with the Siemen Lithostar lithotriptor. The HM3 necessitated general anesthesia in 67 percent of patients and the Lithostar necessitated intravenous sedation in 86 percent. The majority of pediatric lithotripsy treatments were performed on an outpatient basis (24) or during an overnight hospital stay (3) while 8 were done on an inpatient basis. Of the 37 stones treated with 1 ESWL session 68 percent resolved, 19 percent had residual fragments less than 4 mm., 8 percent had residual fragments greater than 4 mm. and 5 percent required an endoscopic procedure for resolution. When success rates by lithotriptor were examined no significant difference between the 2 machines was identified although the HM3 treated larger stones (p = 0.0499). There were no statistical differences in regard to success and the use of stents, patient age or stone location between the 2 lithotriptors. Three patients required adjuvant procedures, and complications and morbidity developed in 2 and 5, respectively. All children or parents were contacted for followup (range 7 to 67 months). One child required ESWL for a new stone while another passed a stone without intervention. Only 1 child with a residual fragment less than 4 mm. became symptomatic but needed no intervention while 1 of 3 with fragments greater than 4 mm. needed intervention. No patients required open or percutaneous intervention.