The last of the Mohicans

Reminiscences and ideas of a Member (formerly Associate Fellow) of the American Society of Colon and Rectal Surgeons and especially one of the Last of the Mohicans presently (apology to James Fenimore Cooper).     

Characterization of HIV-1 neutralization escape mutants

Infection by molecularly cloned HIV-1, in the presence of a high-titre neutralizing monoclonal antibody (MAb), resulted in the selection of plaques in MT4 cells releasing HIV resistant to neutralization by the same MAb. The epitope recognized by the MAb was mapped to the V3 neutralization epitope at amino acids 305-321. The HIV-1 variants showed a reduced binding capacity for the selecting MAb as determined by immunofluorescence. Polymerase chain reaction (PCR) amplification of complementary DNA derived from viral RNA, cloning and sequencing identified a base pair (bp) change C----G at position 6663 in variant 110.5/1, predicting a change at amino acid 308 Arg----Gly. No other changes in the epitope were observed by sequencing three other variants. Differential hybridization of PCR amplified viral RNA and DNA, with oligonucleotides specific for the observed bp change or the 'wild type' sequence, indicated that the variants 110.5/1 and 110.5/7 were genotypically mixed for 308Gly/Arg. Subsequent screening of biologically 'recloned' variants 110.5/1 and 110.5/7 identified two subclones homozygous for the 308Gly change. The Arg----Gly change appears to affect the binding of the antibody to the epitope, since the linear peptide substituting 308Gly for 'wild type' 308Arg was 100 times less potent in blocking the neutralization of parental HIV. Amino-acid residue 308 thus appears to be crucial for antibody binding to the epitope. In addition, mutations distant from the monoclonal antibody binding site may also affect neutralization by antibodies recognizing the V3 loop.     

Splenic injury: a 5-year update with improved results and changing criteria for conservative management

The policy of conservative nonoperative management of the injured spleen is reviewed, and recommendations are made to improve this mode of therapy. From 1981 to 1986, 75 patients were admitted with diagnosed splenic injury. Of thes, ten were operated on (four splenorrhaphies, three total splenectomies, one partial splenectomy; in two, the spleen had stopped bleeding spontaneously) and three died, all from causes unrelated to splenic trauma. Only 23% of the patients treated nonoperatively required blood transfusions, and the length of both hospital stay and time spent in the ICU was reduced. The results of this review show that, in comparison with our previous 5-year report, the number of patients treated without surgery increased from 70% to 87%, those receiving blood transfusions decreased from 36% to 23%, and the number undergoing a splenectomy decreased from 24% to 4%. These data suggest that almost all children with splenic injury can be successfully treated without an operation, those who are hemodynamically stable do not require ICU care, and the total hospital stay for uncomplicated splenic injury can be limited to seven days. A laparotomy can be safely reserved for patients with immediate massive hemorrhage or with transfusion requirements of greater than 40 mL/kg.