Activity of (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC) against guinea pig cytomegalovirus infection in cultured cells and in guinea pigs

(S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine, HPMPC, and two HPMPC-related nucleoside analogs, (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine, HPMPA, and (2-phosphonylmethoxyethyl)guanine, PMEG, were evaluated for their antiviral activities against guinea pig cytomegalovirus (GPCMV) infection in guinea pig embryo (GPE) cells and human cytomegalovirus (HCMV) infection in human diploid fibroblast (MRC-5) cells. DHPG, 9-(1,3-dihydroxy-2-propoxymethyl)guanine, was used for comparison. The antiviral activity of HPMPC against GPCMV infection in vivo and its toxicity to Hartley guinea pigs were also evaluated. The 50% antiviral effective doses (ED50) of HPMPC, HPMPA, PMEG and DHPG against GPCMV infection in GPE cells were 0.22, 1.4, 0.07 and 62 microM, respectively; and against HCMV infection in MRC-5 cells, the ED50s were 0.51, 0.72, 0.01 and 17.5 microM, respectively. Their cytotoxic doses (CyD50) in GPE replicating cells were 84, 35, 1.4 and 700 microM, respectively and in MRC-5 cells were approximately 114, 31, 0.86 and 750 microM, respectively. Based on their calculated therapeutic indexes, HPMPC was the most potent and selective of the four compounds tested. In vivo, during acute infection, the spleen indexes of all infected animals that were treated with 1.25 to 5.0 mg/kg/day of HPMPC for 5 days were significantly reduced as compared with sham-treated animals. Virus infectivity titers in blood and various tissues of infected animals treated with HPMPC, 2.5 or 1.25 mg/kg/day were not significantly lower than those of the infected, sham-treated animals; with 5 mg/kg/day, infectivity titers in the blood, spleen, and salivary gland were significantly lower in HPMPC-treated than in sham-treated animals. However, HPMPC was toxic to guinea pigs especially at doses of 5 to 10 mg/kg/day. These data showed that HPMPC was highly active and selective in cultured guinea pig cells and human fibroblast cells against CMV infection but did not effectively inhibit GPCMV infection in guinea pigs at minimum toxic concentrations.     

Doppler ultrasonic diagnosis for deep venous thrombosis of lower limbs.

Seventy-one patients with 80 lower limbs clinically suspected of deep venous thrombosis (DVT) were investigated by both Doppler ultrasound and venography. Sixty-seven lower limbs demonstrated by venography to have DVT, in 5 the thrombus was confined to the calf, and all were detected by the Doppler ultrasound. In 62 limbs thrombus extended into the popliteal and more proximal veins, the Doppler ultrasound detected 61 of them, a sensitivity of 98%. Venography showed a deep venous system without any evidence of thrombosis in 13, the Doppler findings were normal in all of the 13 lower limbs, a specificity of 100%. We found that the examination of the popliteal vein with patient in a semi-lateral prone position was important in detecting the presence of thrombosis in popliteal and more proximal vein.

     

Initial experiences with the use of the surgical CO2 laser scalpel

Reported in this paper is the surgical applicability, as established from 35 operations, of the Type TLS 61 laser scalpel of Tungsram Rt, 60 Watt in output. Useful experience has been recorded from surgical approaches to thorax cavity as well as from general, gastro-enterological, vascular, and dermatological surgery. Minimised bleeding and sterile incisions are benefits of laser operations. The above model has proved to be applicable to skin, muscles, lung, stomach, intestines, bones, and other tissues. Wound healing was absolutely okay. After-bleeding or other complications did not occur.     

Preliminary experience of angioscopy in femorodistal bypass.

During femorodistal bypass angioscopy can be used in vein graft preparation allowing valve lysis and the identification of tributaries under direct vision. A total of 30 patients have undergone angioscopic assisted femorodistal bypass using either an Olympus or Stortz system. Nineteen patients have undergone full vein mobilisation and valve lysis under direct vision. Eleven patients had in situ bypass with ligation of tributaries, identified by the angioscope, through small stab incisions. No evidence of fistula or retained valve cusps was found by subsequent duplex scanning and arteriography. One of these grafts failed at 6 days due to an unrecognised outflow stenosis. The mean hospital stay after operation for this latter group of patients was 5.2 days (range 4.4-6.0 days) compared with 9.5 days (8.6-10.3 days) in a historical group of 30 patients (P < 0.001). Angioscopy is a useful aid in the performance of femorodistal bypass. Early experience suggests that hospital stay may be reduced by angioscope assisted in situ femorodistal bypass because of the minimal dissection involved.