Altered regulation of in-vivo coagulation in orthopedic patients prior to knee or hip replacement surgery.

Up to 20% of patients develop venographically proven deep-vein thrombosis after elective orthopedic surgery even under the cover of heparin or low molecular weight heparin. The extent to which the chronic inflammation of osteoarthritis requiring elective orthopedic surgery alters in-vivo coagulation and whether any specific alteration influences the development of postoperative thrombosis are unknown. This study compared the concentrations of activated factor VII (FVIIa), tissue factor pathway inhibitor (TFPI), activated factor X (FXa)-TFPI, thrombin-antithrombin, and prothrombin fragment 1+2 (F1+2) in plasmas of 535 healthy individuals (ages 17-76) with those in the preoperative plasmas of 306 arthritis patients (ages 30-92) scheduled for elective knee or hip replacement surgery. C-reactive protein was also measured in the plasmas of approximately 15% of the participants. Age-adjusted concentrations of FVIIa, F1+2, and C-reactive protein were higher in patients than controls, while the concentrations of thrombin-antithrombin, TFPI and FXa-TFPI were similar. Chronic inflammation in the patients was thus associated with increased coagulation in vivo. Without compensatory increases in the concentrations of TFPI (natural inhibitor of prothrombinase), the elevated concentrations of FVIIa in the preoperative plasmas and the trauma associated with surgery may enhance the risk for developing postoperative deep-vein thrombosis.     

Combined use of cryotherapy and diode laser photocoagulation for the treatment of threshold retinopathy of prematurity.

PURPOSE: Cryotherapy and indirect laser retinal photoablation are both effective in the treatment of retinopathy of prematurity (ROP). We describe the safety, efficiency, and effectiveness of combined cryotherapy and diode laser photocoagulation to treat threshold ROP. METHODS: Records of patients developing threshold ROP from January 1, 1996 through December 31, 1998, were retrospectively reviewed to identify those treated with combined cryotherapy and photocoagulation and followed up for at least 45 days postoperatively. Diode laser was used to ablate posterior avascular retina, and cryotherapy was used for anterior retina. Data reviewed included ocular and systemic complication rates, treatment duration, number of laser burns, most recent fundus examination, visual acuity, and refraction. RESULTS: In 13 patients, 23 eyes received combined treatment. No intraoperative complications occurred. Mean duration of anesthesia and treatment was 35 +/- 8 minutes/eye. A mean of 117 +/- 84 laser burns/eye were applied. In 20 of 23 eyes (87.0%), anatomic outcome was favorable at last examination. In 13 of 16 eyes (81.3%), functional (visual acuity) outcome was favorable (visual acuity better than 20/200) at 1 year. At 6 months or later, 14 of 16 eyes (87.5%) measured were myopic, of which 5 (31.3%) were highly myopic (> 6 diopters). CONCLUSIONS: The effectiveness of treating ROP with combined cryotherapy and diode laser photocoagulation compares with that of either modality alone. By decreasing the number of laser applications, combined therapy may be faster and technically easier for eyes with very posterior ROP. This may decrease the number of complications seen when either excessive cryotherapy or laser retinal photoablation is used.     

Distribution and disposition of trospectomycin sulfate in the in vivo rat, perfused rat liver, and cultured rat hepatocytes

Trospectomycin sulfate is an experimental, aminocyclitol antibiotic. It has been shown in preclinical, chronic safety studies in the dog and rat to elicit a reversible, lysosomal phospholipidosis in liver. The present experiments were conducted to characterize the tissue distribution and disposition of 3H]trospectomycin sulfate in the male rat, perfused rat, perfused rat liver, and cultured rat hepatocytes. Following a 5 mg/kg iv dose to four rats, approximately 70% of the dose was recovered within 24 hr primarily in urine as unchanged drug, and the remainder was eliminated with a terminal phase half-life in blood and tissues of 3 days. Fecal excretion was relatively minor (16% of the dose recovered in feces in 7 days) until later timepoints, when it was the principal pathway of terminal phase elimination. The liver sequestered approximately 10% of the dose and had the highest tissue levels of drug at all times measured. Liver perfusion experiments indicated that trospectomycin accumulated in a hepatic depot compartment as parent drug by a first-order process which was nonsaturable up to a 1 mM concentration of drug. Biliary excretion of unchanged trospectomycin by the perfused liver was slow (approximately 3% of the dose in 2 hr) and occurred by both paracellular and transcellular mechanisms. The hepatic depot compartment appeared to be responsible for transcellular biliary excretion, and thus for the sustained fecal excretion observed in vivo. Subcellular distribution experiments indicated that at least 50% of the drug in the hepatic depot was sequestered in organelles having a broad density range. The existence of a trospectomycin depot compartment was also demonstrated in cultured hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Olfactory Neuroblastoma and Neuroendocrine Carcinoma of the Anterior Skull Base: Treatment Results at the M.D. Anderson Cancer Center

Updated information on the pathologic characterization and treatment of olfactory neurobiastoma (ON) and neuroendocrine carcinoma (NEC) diseases is presented. A series of patients with ON or NEC was evaluated and retrospectively staged using the UCLA system. The parameters evaluated were symptoms, age, sex, risk factor assessment, stage of disease, treatment, and clinical outcome. The median follow-up was 3 years (range, 18 months to 23 years). The predominant therapy (63%) for ON was combined surgery and radiotherapy. Surgery alone or in combination with ancillary treatment was used in 58% of patients with NEC. For the most receat years of the study, patients with NEC have been treated successfully with combined chemotherapy and radiotherapy. Seventy percent of the patients with ON and 75% of the patients with NEC were clinically free of disease during the defined follow-up period. Surgical therapy consisting of a craniofacial resection combined with postoperative radiotherapy has resulted in good local and long-term control of ON. Our experience indicates that combined chemoradiation is an appropriate therapeutic approach for NEC.     

Brief chemotherapy, involved field radiation therapy, and central nervous system prophylaxis for paranasal sinus lymphoma.

Lymphoma of the paranasal sinus is a rare tumor characterized by bulky local disease, early systemic dissemination, and a propensity for central nervous system (CNS) spread. Treatment with radiation alone generally has been disappointing. Based on previous encouraging reports of initial brief chemotherapy followed by involved field radiation therapy (IFRT) for localized large cell lymphoma, four consecutive patients with paranasal sinus lymphoma were treated with 6 weeks of chemotherapy followed by IFRT and CNS prophylaxis. All patients had bulky localized disease and diffuse large cell lymphoma. Complete response was seen in all patients, and none have had a relapse (minimum follow-up, 25 months; range, 25 to 32 months). Chemotherapy and radiation therapy were well tolerated. One patient developed an osteogenic sarcoma in the radiation field 32 months after completion of therapy. Administration of early frequent chemotherapy followed by IFRT and CNS prophylaxis appears to be an effective treatment strategy for patients with localized large cell lymphoma of the paranasal sinuses.     

INVOLVEMENT OF NON-NMDA AND NMDA RECEPTORS IN GLUTAMATE-INDUCED PRESSOR OR DEPRESSOR RESPONSES OF THE PONS AND MEDULLA

1. Fifty-five intact and six baroreceptor denervated and vagotomized cats of either sex were anaesthetized intraperito-neally with urethane (400 mg/kg) and a-chloralose (40 mg/kg). Responses of the systemic arterial pressure (SAP), mean SAP (MSAP) and sympathetic vertebral nerve (VNA) and renal nerve activities (RNA) were recorded. 2. In intact animals, monosodium L-glutamate (Glu, 0.1 mol/L, 50 nL) was microinjected into pressor areas of the locus coeruleus (LC), gigantocellular tegmental field (GTF), rostral ventrolateral medulla (RVLM) and dorsomedial medulla (DM), and the depressor areas of caudal ventrolateral medulla (CVLM). The induced actions were compared before and after microinjection of either glutamate antagonists, glutamate diethylester (GDEE, 0.5 mol/L, 50–100nL), a competitive AMPA receptor blocker, or 2-amino-5-phosphonovaleric acid (D-AP5, 0.025 mol/L, 50–100 nL), a competitive N-methyl-D-aspartate (NMDA) receptor blocker. GDEE completely blocked the increases of SAP and VNA elicited from all pressor areas. D-AP5 only partially blocked the pressor but slightly blocked VNA and RNA responses from LC, GTF and DM, particularly those from RVLM. Neither GDEE nor D-AP5 blocked the depressor responses of SAP and two nerve activities elicited from CVLM. 3. In baroreceptor denervated animals, NMDA (2 mmol/L, 50–100 nL) and AMPA (0.2 mmol/L, 50–100 nL) were micro-injected into the same pressor areas of GTF, RVLM and DM and the depressor area of CVLM responsive to Glu activation (0.1 mol/L, 30 nL). In RVLM, DM and CVLM, the results of either NMDA or AMPA were similar to those induced by Glu. However, in GTF, microinjection of either NMDA or AMPA did not induce similar responses to Glu. This suggests that the nature of GTF may differ from RVLM and DM. 4. The above results suggest that the Glu-induced pressor responses from LC, GTF, DM and especially RVLM, are primarily mediated through AMPA receptors. The Glu-induced depressor responses from CVLM may not be predominantly mediated by either AMPA or NMDA receptors. 5. In both baroreceptor-intact and -denervated cats stimulation of the pressor areas often produced an increase of VNA and a decrease of RNA, while in the depressor CVLM decreased both VNA and RNA. The VNA, but not RNA were positively correlated with the pressor responses, while both VNA and RNA were positively correlated with the depressor responses. This may suggest that neurons of the sympathetic vertebral and renal nerves are topographically organized in the brain.     

Kappa 3 receptors and levorphanol-induced analgesia.

Levorphanol is a widely used opiate analgesic. Although structurally related to morphine, levorphanol has high affinity for a number of receptor subtypes, including both kappa 1 and kappa 3. Prior reports had implicated a kappa component of levorphanol-induced antinociception. Evidence is now presented suggesting that levorphanol-induced analgesia is produced by a mixture of mu and kappa 3 mechanisms. Levorphanol was a potent analgesic in the tail-flick assay, when given systemically, spinally or supraspinally. Isobolographic analysis of the combined administration of levorphanol, spinally and supraspinally implied synergistic interactions. Naloxonazine reduced levorphanol-induced analgesia, implicating a role for mu1 receptors. The kappa 1 antagonist nor-binaltorphimine at a dose which reversed analgesia induced by U50,488H did not antagonize levorphanol-induced analgesia. Additional studies revealed no cross tolerance in either direction, between levorphanol with the kappa 1 analgesic U50,488H. Together, these results strongly argue against a role for kappa 1 receptors in levorphanol-induced analgesia. However, mice tolerant to the kappa 3 analgesic, naloxone benzoylhydrazone (NalBzoH), showed cross tolerance to levorphanol, implying a role of kappa 3 mechanisms in levorphanol-induced analgesia.     

Proximal femoral focal deficiency: radiologic analysis of 49 cases

Proximal femoral focal deficiency, an uncommon congenital anomaly, necessitates early radiologic classification for surgical planning and treatment. Objective radiographic criteria, including femoral length index, acetabular depth index, acetabular angle index, and shape of the proximal femur were determined in 49 patients before cartilaginous ossification of the femoral capital epiphysis; final classification was based on follow-up radiographs or findings at arthrography or surgery. These parameters were analyzed to determine the accuracy and contributions of each in classification. Correct classification into one of three groups was possible in 86% of cases with use of three of the parameters: femoral length index, acetabular depth index, and shape of the proximal femur. The acetabular angle was found to contribute insignificantly to classification. Magnetic resonance imaging, used in only one case, depicted the nonossified cartilaginous femoral capital epiphysis, thus obviating the need for invasive diagnostic procedures and facilitating early classification.