Ankle arthrodesis: combined internal-external fixation.

This report documents the experience of using combined internal and external fixation in ankle arthrodesis. During the period from 1992 to 2000 a single surgeon used this method of fixation on 26 ankle fusions in 26 consecutive patients without exclusions. There were no nonunions and no delayed unions. The median time to union was 10.3 weeks and the mean time was 11.3 weeks (range, 7.4 to 23.2 weeks). Complications specific to this procedure included 3 (12%) minor pin tract infections which cleared with oral, out-patient antibiotics, 4 (15%) skin irritations from internal fixation pins sufficiently bothersome to require pin removal after union was obtained, and 1 (4%) painful pin tract which cleared spontaneously. Most of these complications occurred early in the series and subsequent changes in technique considerably decreased their incidence. This fixation technique produced excellent results. Combined internal and external fixation is recommended as a useful option in arthrodesis of the ankle.

Interdigital neuroma: intermuscular neuroma transposition compared with resection.

This prospective, randomized study compares the treatment of an interdigital neuroma (IDN) by the standard resection operation with a technique in which the IDN is transposed into the inter-muscular space between the adductor hallucis and the interossei muscles after division of the digital nerves distal to the IDN. The resection group contained 22 patients and 22 neuromas and the transposition group contained 22 patients and 23 neuromas. An interviewer, blinded as to the operative technique used, telephoned each patient preoperatively, and at 1 month, 3 months, 6 months, 12 months, and 36-48 months postoperatively. The interviewer recorded the patient's reported pain level on a numerical rating scale of 0 to 100. In the resection group the average pain level was slightly lower through the first 6 month period, but at the 12 month review the resection group had a slightly higher average pain level . At the 36-48 month survey the resection group again reported a greater average pain level and fewer asymptomatic patients. It was concluded that it is unnecessary to excise the IDN to obtain excellent relief of pain. It was also concluded that transposition of the IDN into an intermuscular position between the adductor hallucis and the interossei muscles produced significantly better long term results than did the standard resection operation.

HIV-1 genotypic zidovudine drug resistance and the risk of maternal--infant transmission in the women and infants transmission study. The Women and Infants Transmission Study Group.

OBJECTIVES: Although the treatment of pregnant women and their infants with zidovudine (ZDV) has been remarkably effective in preventing the perinatal transmission of human HIV-1, many potentially preventable infections still occur. To examine whether the risk of perinatal infection is increased among women who carry ZDV-resistant HIV-1, the role of genotypic ZDV resistance in perinatal transmission was evaluated. METHODS: The reverse transcriptase (RT) region of clinical isolates from culture supernatants of 142 HIV-1-infected women enrolled in the Women and Infants Transmission Study (WITS), who had been treated with ZDV during pregnancy was sequenced. Results from genotypic sequencing were linked to demographic, laboratory, and obstetrical databases, and the magnitude of association of having consensus drug-resistant HIV-1 RT mutations with transmission was estimated. RESULTS: Twenty-five per cent (34/142) of maternal isolates had at least one ZDV-associated resistance mutation. A lower CD4 cell percentage and count (P= 0.0001) and higher plasma HIV-1 RNA (P=0.006) were associated with having any ZDV resistance mutation at delivery. Having any RT resistance mutation [odds ratio (OR): 5.16; 95% confidence interval (CI): 1.40, 18.97; P=0 0.01], duration of ruptured membranes [OR: 1.13 (1.02, 1.26) per 4 h duration; P= 0.02], and total lymphocyte count [OR: 1.06 (1.01, 1.10) per 50 cells higher level; P=0.009] were independently associated with transmission in multivariate analysis. CONCLUSION: Maternal ZDV resistant virus was predictive of transmission, independent of viral load, in these mothers with moderately advanced HIV-1 disease, many of whom had been treated with ZDV before pregnancy.

A combinatorial ledge: reverse transcriptase fidelity, total body viral burden, and the implications of multiple-drug HIV therapy for the evolution of antiviral resistance.

The chronicity, high mutation rates, and high circulating titers of HIV during the 'stable' phase of infection make rapid evolution of resistance mutations a key predictor of antiretroviral efficacy. Recent advances in measurement of viral RNA titers, turnover dynamics and the in vivo spectrum of resistance mutations allow realistic in vivo estimates of important kinetic parameters of within-patient evolution of viral resistance. First-order estimates of the frequency of viral genotypes necessary for resistance to many antiretroviral combination regimens indicate that many such genotypes pre-exist in patients prior to initiation of therapy. The combinatorial nature of observed multiply-resistant genotypes, however, along with current estimates of total-body viral load and viral turnover dynamics, imply a strikingly sharp transition associated with the change from two-drug to three-drug antiretroviral regimens: pre-existing resistance being near-certain in the first instance but highly unlikely in the second. This abrupt change, a 'combinatorial ledge', carries with it a number of important implications for the understanding and control of HIV infection and other potential targets of antiviral therapy.

Selective vertical transmission of HIV-1 antiretroviral resistance mutations.

OBJECTIVE: To examine the patterns of vertical transmission of zidovudine (ZDV) resistance mutations. DESIGN: HIV-1 reverse transcriptase codons 10-250 were sequenced from 24 pairs of ZDV-exposed women and their HIV-infected infants as part of the Women and Infants Transmission Study. METHODS: Viral RNA was extracted from tissue culture supernatants and sequenced using fluorescent dye-primer chemistry and an automated sequencer. RESULTS: For 17 of these pairs, maternal and infant sequences were identical to one another and lacking known ZDV resistance mutations. The remaining seven maternal sequences contained known mutations associated with ZDV resistance at reverse transcriptase codons 70, 210, 215 and 219. In each case where the maternal HIV isolate showed a pure mutant species, the infant sequence was identical. When the maternal sequence showed the presence of a sequence mixture at codon 70 or 219, the infant's virus showed only wild-type sequence even when the ZDV-resistant mutant was quantitatively dominant in the mother. The single maternal HIV isolate showing mixed sequence at codon positions 210 and 215 transmitted an unmixed mutant to the infant at both positions. When maternal mixtures were present at sites not associated with ZDV resistance, only the dominant species appeared in the infant. CONCLUSIONS: When maternal HIV isolates contained mixed wild-type and ZDV-resistant subpopulations, only a single component of the mixture could be detected in the infected infants. Resistance mutants without the codon 215 mutation were not transmitted from mixtures, even when the mutants formed the majority of circulating maternal virus. In perinatal HIV transmission, specific ZDV-resistant HIV genotypes circulating in the maternal virus pool may influence whether infection in the infant will be established by a wild-type or ZDV-resistant HIV strain.

Avascular necrosis of the first metatarsal head: incidence in distal osteotomy combined with lateral soft tissue release.

The incidence of avascular necrosis of the metatarsal head following distal first metatarsal osteotomy combined with adductor tendon release has not been documented in a large series of patients. Of 82 consecutive procedures in 64 patients performed between 1986 and 1988, 42 patients (58 procedures) were available for clinical and radiographic examination. Average follow-up was 2.5 years (range 1.0-4.2 years). There were 35 L-shaped and 23 chevron osteotomies which were combined with a lateral soft tissue release that included adductor tenotomy. Preoperative hallux valgus angle averaged 25 degrees (range 15-40 degrees), and intermetatarsal angle averaged 12 degrees (range 5-24 degrees). Follow-up amount of correction averaged 13 degrees and 5 degrees, respectively. Eighty-four percent of patients were satisfied with their result. There was one case of avascular necrosis. The patient was asymptomatic at 4.2 years' follow-up, and the remaining patients included two with infections, one hallux varus, and no nonunions.

Transcriptional activation of homologous and heterologous genes by the hepatitis B virus X gene product in cells permissive for viral replication.

The potential of the hepadnavirus X gene product to activate gene expression in trans was tested through a series of cotransfections of X expression vectors with a variety of potential targets for transactivation. The X gene products from human hepatitis B virus (HBV), woodchuck hepatitis virus, and ground squirrel hepatitis virus are all equally active in augmenting the expression of a wide array of target promoters in both permissive and nonpermissive cells. Using the HBV genome itself as the source of X protein, we demonstrate that transactivation of HBV and heterologous genes occurs when X protein is expressed in its native state during productive infection of permissive cells. Run-on transcription analysis indicates that this transactivation occurs at the level of primary transcription.

Replication of duck hepatitis B virus in two differentiated human hepatoma cell lines after transfection with cloned viral DNA.

Cloned DNA of duck hepatitis B virus (DHBV) was used to transfect two differentiated human hepatoma cell lines, Huh 7 and Hep G2. Use of the transfected genome as a transcriptional template was demonstrated by the appearance of virus-specific subgenomic and genomic transcripts. Comparison of the steady-state ratio of subgenomic to genomic transcripts in Huh 7 and Hep G2 cells suggests that there are differences in the relative stability and/or rate of production of these transcripts between these cell lines. Viral genomic replication proceeded in both lines, as judged by the presence of DHBV DNA replicative intermediates in cytoplasmic core particles; the levels of these replicative intermediates is roughly equivalent in Huh 7 and Hep G2 cells. Subcutaneous injection of tissue culture medium from transfected Huh 7 cells into Pekin ducks resulted in productive DHBV infection, indicating the production and export of biologically active virus. These cell lines should provide a valuable system for studying the molecular mechanisms of the hepadnaviral life cycle.