Administration to humans of ORG 21465, a water soluble steroid i.v. anaesthetic agent

Ten male volunteers received a 1-min i.v. infusion of a new water soluble steroid anaesthetic agent, ORG 21465. Individuals received doses ranging from 0.8 to 1.8 mg kg-1. All subjects experienced venous pain at the site of injection; those receiving 1.0 mg kg-1 or more became anaesthetized. There was no evidence of histamine release and apnoea did not occur. Excitatory phenomena were observed in all subjects and were dose related; no spikes were seen on the EEG. Pharmacokinetic analysis supported a three-compartment (non-weight- related) model with compartmental volumes V1, V2 and V3 of 4.31, 14.2 and 89.4 litre, respectively. Clearance from the central compartment V1 was 1.55 litre min-1. Inter-compartmental clearances Q1 and Q2 were 2.54 and 1.79 litre min-1. We found that ORG 21465 was an effective anaesthetic in humans. The relationship between sedation, anaesthesia and excitation requires further exploration.      

The role of arthroscopic surgery in the evaluation of acute traumatic hemarthrosis of the knee

Eighty patients presented for evaluation with an acute traumatic hemarthrosis of the knee and negligible instability on clinical examination. All had an examination under general anesthesia followed by arthroscopy. Anatomical lesions were demonstrated in 71 of 80 knees (89%) including anterior cruciate ligament (ACL) disruption in 50 (62%). Twenty-nine of 50 patients (58%) with arthroscopically-demonstrated ACL injuries had associated meniscal tears. Fifteen (19%) demonstrated isolated meniscal tears and nine (11%) osteochondral fractures not detected by conventional roentgenograms. The frequent occurrence of injuries to other joint structures in conjunction with ACL injuries was remarkable. An acute traumatic hemarthrosis of the knee often masks significant lesions. Arthroscopy aids the orthopedic surgeon in determining the full extent of the intraarticular damage.     

Natural history and treatment of anorectal strictures complicating Crohn's disease

Forty-four patients seen between 1975 and 1985 with anorectal strictures complicating Crohn's disease have been reviewed to determine the natural history and outcome of surgical treatment. Proctitis was present in 98 per cent, and 93 per cent of patients had sever perianal disease. The site of strictures was rectal in 22, anal in 15 and anorectal in 11 (4 patients had a stricture at 2 sites). Initial treatment was by rectal excision alone in 6, dilatation in 33, and 5 needed no treatment at all. Single dilatation was effective in 15, 8 required two dilatations and in 10 repeated dilatation was necessary. Proctocolectomy was eventually required in 19 patients, 2 have a loop ileostomy and 1 has an ileostomy with a rectal stump in situ. Only 21 remain asymptomatic while 3 continue to need dilatation. Perineal wound healing was delayed in 9 of 19 patients having a proctocolectomy and in 3 the perineal wound has never healed.     

Retraction brain ischaemia: mannitol plus nimodipine preserves both cerebral blood flow and evoked potentials during normoventilation and hyperventilation.

In our miniature swine model simulating operating room brain retraction, we investigated the effects of mannitol plus nimodipine on cerebral blood flow (CBF) and evoked potentials (EP) ipsilateral and contralateral to retraction, in comparison with either agent alone, during both normoventilation and hyperventilation. We here report results in 27 animals with intravenous mannitol (2 g kg-1 over 15 min) and/or nimodipine (1 microgram kg-1 min-1 constant infusion). Mannitol plus nimodipine was superior both to controls and to either mannitol alone or nimodipine alone in preserving EP amplitude ipsilateral to retraction during both normoventilation and hyperventilation. Mannitol alone was effective in normoventilation at preserving EP, while nimodipine alone was effective in hyperventilation. No significant asymmetries in CBF or EP were seen with mannitol plus nimodipine in either normoventilation or hyperventilation. By five minutes postretraction CBF had returned to preretraction values for all groups, and EP amplitude had returned also except for hyperventilated controls. In this model of brain retraction, mannitol plus nimodipine is superior to either agent alone in maintaining both CBF and EP when normoventilation and hyperventilation are employed. The results are discussed in terms of the possible mechanisms for the different and complementary effects of mannitol and nimodipine.     

Relative disease severity in siblings with myotonic dystrophy.

Myotonic dystrophy is an autosomal dominant disorder in which an early-onset form is characteristically inherited from the mother. We studied 17 affected sibling pairs from 15 families in which two or more affected children were born to mothers with myotonic dystrophy. Later-born affected children suffered more severe disease than their first-born siblings in 13 of 17 sibling pairs. Later-born affected siblings displayed significantly more neonatal feeding difficulties, later age when first sitting alone, later age when first walking alone, and a higher incidence of scoliosis. The overall difference in disease severity between affected siblings increased as the age difference between them increased, suggesting that increasing maternal age is a factor in the relative disease severity of affected children. These findings may have relevance for genetic counseling.     

Purification of a terminal uridylyltransferase that acts as host factor in the in vitro poliovirus replicase reaction.

Poliovirus RNA polymerase requires a host factor to initiate RNA synthesis in vitro. The host factor was previously purified to near homogeneity from HeLa cells but was not assigned an enzymatic activity. This report describes the purification of a terminal uridylyltransferase that can act as host factor. By all criteria examined it is identical to the factor purified previously. It has the same molecular weight (68,000), chromatographic properties, and cellular localization. We present evidence that terminal uridylyltransferase can add uridine residues to the 3' poly(A) end of virion RNA and that these anneal back to the poly(A) and form a hairpin primer for polymerase.     

Prenatal ultrasound diagnosis of fetal candida infection: a complication of a retained intrauterine contraceptive device.

A 32-year-old woman was referred complaining of abdominal pain and bleeding at 18 weeks' gestation. The striking finding on ultrasound examination was of symmetrically enlarged echogenic fetal lungs. In addition, mediastinal compression, increased echogenicity of the kidneys and bowel, an enlarged liver of decreased echogenicity, and hydrops fetalis, as evidenced by ascites and skin edema, were all present. The differential diagnosis included upper respiratory tract obstruction and cystic kidney disease. The presence of fetal hydrops together with the other findings suggested a poor outcome, and on these grounds therapeutic abortion was recommended and performed. Subsequent postmortem findings explained all the ultrasound abnormalities on the basis of extensive fetal candida infection. The presence of a retained intrauterine contraceptive device was considered to be the likely cause and the implications of this, together with the ultrasound abnormalities and differential diagnoses, are discussed.