Synthesis of N-(phosphonoacetyl)-dipeptide derivatives and evaluation of their antihypertensive activity

A series of N-(phosphonoacetyl)-dipeptide derivatives was synthesized for pharmacological testing as antihypertensive compounds. Several of these compounds demonstrated a moderate antihypertensive effect in Wistar spontaneous hypertensive rats (SHR) with p.o. dosing. ACE inhibition by the compounds was studied using ACE from rat plasma and lung. Inhibitors containing esterified C-termini are pro-drugs and showed activity only for plasma ACE.     

Delayed neuropathy and acute toxicity studies with pirimiphos-methyl in the hen

This paper describes studies aimed at determining the acute anticholinergic and delayed neurotoxic potential of the organophosphate insecticide pirimiphos-methyl (O-2-diethylamino-6-methylpyrimidin-4-yl O,O-dimethyl phosphorothioate) in the hen. Delayed neuropathy was assessed by biochemical measurement of neuropathy target esterase (NTE) activities in the brain and spinal cord, clinical signs of neuropathy over two 21-day periods and histological assessment of nervous tissue. Acetylcholinesterase (AChE) activity was also determined in the brain and spinal cord. Hens were given a single oral dose of 100 mg kg-1 pirimiphos-methyl, which was followed by a repeated dose after 21 days. Tri-o-cresyl phosphate (TOCP), 500 mg kg-1, was used as a positive control. All pirimiphos-methyl-treated hens received prophylactic doses of N-methylpyridinium-2-aldoxime methanesulphonate (P2S) and atropine sulphate. Hens dosed with pirimiphos-methyl had very low AChE activities (less than 20% of control) in both the brain and spinal cord, 24 and 48 h after dosing. In the TOCP-treated hens, the activities were about 90% of control. NTE activities in the brain and spinal cord of pirimiphos-methyl-treated hens were identical to those in the controls, while they were profoundly inhibited (greater than 80%) in the TOCP-treated hens. All hens dosed with pirimiphos-methyl showed the expected signs of AChE inhibition and, following recovery, usually by Day 5, no clinical signs of delayed neuropathy were seen. The TOCP-treated hens developed clinical signs of neuropathy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical study on norfloxacin in children

Norfloxacin (NFLX, AM-715), a new synthetic antibacterial agent, was administered to 18 child patients with infectious diseases. The patients included 5 boys and 13 girls from 3 to 14 years of ages. They were given orally dosage ranging 5.2-17.9 mg/kg/day for 4 to 14 days. Clinical efficacies were excellent in 1 case, good in 16 cases, unknown in 1 case, hence the total efficacy rate was determined to be 100%. There were no cases which showed side effects of the drug and no abnormal laboratory test values were observed during the treatment.     

Embryonic and maternal heat shock responses to a teratogenic hyperthermic insult

Exposing embryos to elevated temperatures both in vivo and in vitro has been shown to result in the production of offspring with severe congenital abnormalities. While a direct effect of heat cannot be excluded, recent interest has been focused on the possible role that the induction of the heat shock response may have in the etiology of the observed congenital defects. In the present study, mouse embryos from inbred strains known to differ in terms of their sensitivity to heat-induced exencephaly were treated in vivo and their heat shock response determined using SDS-PAGE electrophoretic techniques. Further, the embryonic responses were compared with a maternal cell type. We observed excellent agreement between the two test systems following exposure to a teratogenic hyperthermic insult. Both the embryonic and maternal cells underwent a reduction in total protein synthesis and an enhanced synthesis of four heat shock proteins migrating with the molecular weights of 68, 70, 97, and 110 kDa. The results failed to indicate any strong correlation between the heat shock response and enhanced genetic sensitivity to hyperthermia-induced neural tube defects.     

Economies of scale, physician volume for urology patients, and DRG prospective hospital payment system

Diagnosis Related Group (DRG) hospital payment has begun to squeeze hospitals financially and is likely to do so in the future. This study analyzed the relationship between the volume of urologic procedures by an individual urologist, hospital costs per patient, and outcome. We used a three-year DRG database of urology patients (N = 2,980) at an academic medical center to analyze these. Low-volume urologists (arbitrarily defined by us) had higher hospital costs per patient, financial losses versus profits under DRGs, and a poorer outcome when compared with high-volume urologists. Pearson correlation showed a positive relationship between cost per patient and physician volume for nonemergency patients (-0.129, p less than 0.0001) and emergency patients (-0.368, p less than 0.0001). This may have been explained (in part) by a greater severity of illness for patients of low-volume urologists. These findings suggest, however, that the volume of urologic procedures per urologist may be related to hospital resource consumption. The health care financing environment of the future should provide substantial interest in this finding for those involved in the consumption of urologic services.     

Isolated neuropraxy of the musculocutaneous nerve

Authors describe a case of isolated posttraumatic neuropraxy of the musculocutaneous nerve. With the presentation of this very rare case attention is called, based on literary date, to the fact that the above injury can be mixed with the distal tendon rupture of the biceps.     

Syndesmosis transfixation screw

Instability of the distal tibia-fibular joint necessitates the implant of a fibular tibial transfixation screw. The screw should be placed 2 cm above the anterior syndesmosis. The angle of insertion is 30 degrees upwards from dorsal in relation to the frontal plane. If tibiofibular stability cannot be maintained following anatomical reconstruction of the fibula the transfixation screw must engage the medial tibial cortex. This is imperative, since the transfixation screw cannot withstand the biomechanical forces during motion and bearing of load if the screw penetrates only three corticals.     

A comparison of the Brooker-Wills and Russell-Taylor nails for treatment of patients who have fractures of the femoral shaft

Seventy-three fractures of the femoral shaft (seventy patients) were randomized to treatment with interlocked nailing with either the Brooker-Wills femoral nail (thirty-nine fractures) or the Russell-Taylor femoral nail (thirty-four fractures). Sixty-one patients (sixty-four fractures) were prospectively followed from admission until healing of the fracture. Specific attention was paid to recording operative details, including technical difficulties associated with insertion of the nails. Technical difficulties were encountered in insertion of the proximal screw, distal screw, and nail, and in deployment of the fins. Insertion of the Russell-Taylor nail was associated with less technical difficulty, operative time, and estimated loss of blood. The two nails differ in their biomechanical properties, methods of fixation, and instrumentation. These differences did not affect the clinical outcome; the fractures in both groups of patients healed with excellent functional results.