Delayed neurotoxicity of diisopropylfluorophosphate (DFP): autoradiographic localization of high-affinity [3H]DFP binding sites in the chicken spinal cord

The delayed neurotoxic organophosphate, diisopropylfluorophosphate (DFP) binds with high affinity to membrane-bound proteins from chicken nerve tissues. The autoradiographic distribution of [³H]DFP binding sites in spinal cord sections of chicken showed higher concentrations of binding sites in gray matter than in white matter. In the cervical region, fairly high densities of [³H]DFP binding sites were found in laminae X and to a lesser extent, in the ventral horn gray matter. To identify the membrane-associated DFP-binding proteins, detergent-solubilized membranes were labeled widi 5-10nM [³H]DFP (10pmol/mg protein) for 70 min at 37°C. Gel-exclusion chromatography of the [³H]DFP-radiolabeled membranes indicated at least two major radioactive proteins with apparent molecular weights of 150-670 kDa and 40-129 kDa. Although we could not identify the high affinity DFP binding proteins, the autoradiographic experiments clearly demonstrated that the DFP binding proteins localized on gray matter of chicken spinal cord.     

Effect of rotational alignment on patellar tracking in total knee arthroplasty

Forty-four consecutive patients (65 knees) who underwent identical condylar type total knee arthroplasty were evaluated retrospectively. In 22 of the patients (32 knees), the femoral component was set parallel to the posterior condylar axis (neutrally aligned group). In the remaining 22 patients (33 knees), it was set in an external rotation position of 3 degrees to 5 degrees relative to the axis (externally aligned group). Of the total knee arthroplasties in the neutrally aligned group, 34% required lateral release, compared with only 6% in the externally aligned group; patellar tracking in the externally aligned group was significantly better than that in the neutrally aligned group. Postoperative measurements performed using computed tomography scans showed that the mean angle between the prosthetic posterior condylar axis and the transepicondylar axis was 7.9 degrees in the neutrally aligned group and 3.2 degrees in the externally aligned group. The external rotation setting of the femoral component diminished the need for lateral retinacular release and may decrease the rate of patellofemoral complications that occur after total knee arthroplasty.     

Bone Metastases from Soft Tissue Sarcomas

The incidence, distribution, time of appearance, and radiologic findings of bone metastases from soft tissue sarcomas, exclusive of lymphomas, were evaluated in 320 patients with soft tissue sarcomas. Thirty patients (9.4%) had evidence of 58 bone metastases. Five of 30 patients presented with metastases, and 25 of 30 patients developed metastases up to 66 months after presentation with a mean time interval of 21.3 months. The incidence of skeletal metastases differed among histologic subtypes of sarcomas; alveolar soft part sarcoma (5 of 8), dedifferentiated liposarcoma (2 of 4), angiosarcoma (2 of 4), and rhabdomyosarcoma (5 of 16) tended to show a higher incidence of bone metastases. The sarcomas metastasized to the regional bones close to the primary tumor in 16 (53%) of 30 patients and to the axial bones in 18 (60%). On conventional radiographs, the osseous metastases demonstrated predominantly osteolytic changes, and evidence of pathological fracture was observed in 31% of 58 metastases.     

Successful treatment of tracheomalacia associated with esophageal atresia without a tracheoesophageal fistula by aortopexy: Report of a case

Tracheomalacia (TM) is well known as a complication associated with esophageal atresia (EA) and tracheoesophageal fistula (TEF); however, the occurrence of TM requiring surgical treatment in a patient having EA without a tracheoesophageal fistula has never been reported. We describe herein a rare case of TM associated with EA without TEF. Respiratory distress was caused by compression of the trachea by a severely dilated upper esophageal pouch with weakness of the tracheal wall. Aortopexy was performed, and an excellent postoperative result was achieved.     

Knowledge, risk perception of AIDS and reported sexual behaviour among students in secondary schools and colleges in Tanzania.

A questionnaire survey was carried out among 1041 students in secondary schools and colleges in Dar-es-Salaam, Tanzania to evaluate the relationship between HIV-risky sexual behaviour and anti-condom bias, as well as with AIDS-related information, knowledge, perceptions and attitudes. Self-reportedly, 54% of students (75% of the boys and 40% of the girls) were sexually active, 39% had a regular sexual partner and 13% had multiple partners in the previous year. The condom use rate was higher than previous reports. However, 30% of sexually active respondents did not always use condoms (Risk-1 behaviour) and 35% of those with multiple partners in the previous year did not always use condoms (Risk-2 behaviour). Multiple logistic regression analyses indicated that 'sex partner hates condom' had association with both Risk-1 behaviour (OR 2.47; 95% CI 1.58-3.85) and Risk-2 behaviour (OR 2.47; 95% CI 1.10-5.48). 'Use of condom prevents HIV infection' also had association with both Risk-1 behaviour (OR 2.09; 95% CI 1.19-3.67) and Risk-2 behaviour (OR 3.73; 95% CI 1.28-11.03). Students engaging in risky behaviour were aware of the risk, even though they failed to change their behaviour. Reasons for the AIDS epidemic among Tanzanian students and the importance of more effective AIDS education are also discussed.     

Changes in optic nerve head blood flow and retrobular hemodynamics following calcium-channel blocker treatment of normal-tension glaucoma

Background: Because calcium channel blockers reduce vascularresistance, they may have a clinical application in the treatment ofnormal-tension glaucoma (NTG). This study investigates changes inboth the optic disc blood flow and the hemodynamics of retrobulbarvessels in NTG patients after the systemic administration of a calcium channel blocker. Methods: Twelve eyes of 12 NTG patients (meanage 57 6 ± 15.3 years) were examined before and after a 4-weektreatment with 2 mg b.i.d. oral nilvadipine, an L-typc calcium channel blocker. By scanning laser-Doppler flowmetry (SLDF), we obtained the velocity, flow, and volume from within a 10 × 10 pixel windowplaced on the temporal rim region of the optic disc perfusion map. Byultrasound color Doppler imaging (CDI), we measured the peak systolicvelocity (PSV) and the end diastolic velocity (EDV) of the ophthalmicartery (OA), central retinal artery (CRA), nasal posterior ciliary artery (NPCA), and temporal posterior ciliary artery (TPCA). We then calculated a resistance index (RI) for each vessel. Results: After treatment, the flow and velocity of the optic disc blood flow significantly increased (P < 0.05).Nilvadipine also significantly reduced RIs of the CRA, NPCA, and TPCA(P <0 .05), and increased both the PSV of the NPCA and the EDVs of the CRA, NPCA, and TPCA. The percent change in velocity correlated significantly with the percent changes of the CRA RI and NPCA RI. Conclusions: Oral nilvadipine appears to reduce orbital vascular resistance, which consequentlyincreases the optic disc blood flow. Abbreviations.BP – blood pressure;CRA – central retinal artery;CDI – ultrasound color Doppler imaging;EDV – end diastolic velocity;NPCA – short posterior ciliary arteries located nasal to optic nerve;NTG – normal-tension glaucoma;OA – ophthalmic artery;PP – perfusion pressure;PSV – peak systolic velocity;RI – resistance index;SLDF scanning laser-Doppler flowmetry;TPCA – short posterior ciliary arteries locatedtemporal to optic nerve.     

Nocturnal eating/drinking syndrome and neuroleptic-induced restless legs syndrome

Nocturnal eating/drinking syndrome secondary to neuroleptic-induced restless legs syndrome (RLS) occurred under treatment with low-dose haloperidol in a 51-year-old female schizophrenic patient. Polysomnographic investigation showed a low level of sleep efficacy, periodic leg movements, and a strict relationship between nocturnal eating episodes and non-rapid eye movement sleep. Her nocturnal eating and RLS were completely inhibited by clonazepam treatment. To our knowledge, this is the first published case of nocturnal eating/drinking syndrome secondary to neuroleptic-induced RLS.     

Pharmacokinetic study of low- versus high-dose medroxyprogesterone acetate (MPA) in women

The present study was conducted to compare the pharmacokinetics (PK) of low-dose versus high-dose medroxyprogesterone (MPA) as a once-daily oral administration. Of 32 patients, all women, enrolled in this PK study, 18 received 600 mg MPA daily and 14 received 1200 mg daily. Detailed PK data were obtained on day 1 and after more than 4 weeks of MPA treatment. In addition, multiple data for the minimum steady-state concentration (Css min) were analyzed. The MPA serum concentrations were measured by high-performance liquid chromatography. Wide interpatient variability was found in the PK parameters obtained both on day 1 and after more than 4 weeks. There were no clear relationships between the oral dose and the MPA peak concentration (Cmax), area under the time versus concentration curve (AUC), or mean Css min. Weight gains of 10% or more were demonstrated more frequently in the high-dose group (P<0.01). Liver dysfunction (n=5) did not influence the PK of MPA. Five patients demonstrated extremely low AUC and Cmax (<10 ng/ml) values on day 1. Phenobarbital, dexamethasone and betamethasone were being taken concomitantly with the MPA each by one patient. The serum MPA concentrations were markedly increased after the discontinuation of phenobarbital in that patient, suggesting a drug interaction. At present we cannot recommend the high dose of MPA, except in clinical studies, from a PK or a pharmacodynamic points of view. Received: 2 May 1997 / Accepted: 13 October 1997     

Pain and Bradykinin Receptors--sensory transduction mechanism in the nociceptor terminals and expression change of bradykinin receptors in inflamed condition]

Bradykinin (BK), an endogenous algesic and sensitizing substance, excited nociceptors and sensitized their heat responses. These effects were mediated by B2 receptors (B2Rs) in normal condition, and B1 receptors were additionally recruited in inflammation. B2Rs were coupled with Gq/11 and their activation resulted in diacylglycerol and inositol triphosphate release. Diacylglycerol activated protein kinase (PK) Cepsilon in sensory neurons. To clarify what channel was modulated by PKC to depolarize nociceptor terminals, we examined the heat activation threshold (Tt) of heat-sensitive capsaicin receptor (TRPV1). Tt was lowered down to 31 degrees C by BK in concentration dependent manner through activation of PKCepsilon in cells heterologously expressing TRPV1 and B2Rs. Thus both excitation and sensitization to heat could be explained by one mechanism, lowering Tt of TRPV1. The same was observed in capsaicin-sensitive primary sensory neurons. However, TRPV1 knockout mice showed almost no change in BK-induced nociceptive behavior and nociceptor excitation, although BK-induced heat hyperalgesia completely disappeared, suggesting that TRPV1 was not the sole channel that was modulated by BK to depolarize nociceptor terminals. In addition nociceptor sensitivity to BK was augmented in inflamed animals, with B2R mRNA and protein upregulated. The mechanism for prostaglandin-induced augmentation of BK response is left open for future study.