Popliteal artery trauma. Systemic anticoagulation and intraoperative thrombolysis improves limb salvage

OBJECTIVE: This study was conducted to evaluate those factors associated with popliteal artery injury that influence amputation, with emphasis placed on those that the surgeon can control. SUMMARY BACKGROUND DATA: Generally accepted factors impacting amputation after popliteal artery injury include blunt trauma, prolonged ischemic times, musculoskeletal injuries, and venous disruption. Amputation ultimately results from microvascular thrombosis and subsequent tissue necrosis, predisposed by the paucity of collaterals around the knee. METHODS: Patients with popliteal artery injuries over the 10-year period ending November 1995 were identified from the trauma registry. Preoperative (demographics, mechanism and severity of injury, vascular examination, ischemic times) and operative (methods of arterial repair, venous repair-ligation, anticoagulation-thrombolytic therapy, fasciotomy) variables were studied. Severity of extremity injury was quantitated by the Mangled Extremity Severity Score (MESS). Amputations were classified as primary (no attempt at vascular repair) or secondary (after vascular repair). After univariate analysis, logistic regression analysis was performed to identify the independent risk factors for limb loss. RESULTS: One hundred two patients were identified; 88 (86%) were males and 14 (14%) were females. Forty injuries resulted from blunt and 62 from penetrating trauma. There were 25 amputations (25%; 11 primary and 14 secondary). Patients with totally ischemic extremities (no palpable or Doppler pulse) more likely were to be amputated (31% vs. 13%; p < 0.04). All requiring primary amputations had severe soft tissue injury and three had posterior tibial nerve transection; the average MESS was 7.6. Logistic regression analysis identified independent factors associated with secondary amputation: blunt injury (p = 0.06), vein injury (p = 0.06), MESS (p = 0.0001), heparin-urokinase therapy (p = 0.05). There were no complications with either heparin or urokinase. CONCLUSIONS: Minimizing ischemia is an important factor in maximizing limb salvage. Severity of limb injury, as measured by the MESS, is highly predictive of amputation. Intraoperative use of systemic heparin or local urokinase or both was the only directly controllable factor associated with limb salvage. The authors recommend the use of these agents to maximize limb salvage in association with repair of popliteal artery injuries.     

Synthesis of protected guanidinium linked dinucleoside incorporable into an oligonucleotide using solid phase DNA methodology

The synthesis of novel fully protected guanidinium linked dinucleoside for incorporation into oligonucleotide using solid-phase DNA synthesis methodology was developed. The three different protecting groups selected allow different deprotection conditions.     

True malignant mixed tumor (carcinosarcoma) of tonsillar minor salivary gland origin: diagnostic imaging and endovascular therapeutic embolization

We report a case of carcinosarcoma of the minor salivary glands of the left palatine tonsil, an especially rare location. Imaging characteristics assessed at CT, MR imaging, and angiography are presented. In addition, we describe our experience with preoperative therapeutic endovascular embolization of this hypervascular tumor.     

Identification of trans-acting genes necessary for centromere function in Drosophila melanogaster using centromere-defective minichromosomes

Deletions in the Drosophila minichromosome Dp1187 were used to investigate the genetic interactions of trans-acting genes with the centromere. Mutations in several genes known to have a role in chromosome inheritance were shown to have dominant effects on the stability of minichromosomes with partially defective centromeres. Heterozygous mutations in the ncd and klp3A kinesin-like protein genes strongly reduced the transmission of minichromosomes missing portions of the genetically defined centromere but had little effect on the transmission of minichromosomes with intact centromeres. Using this approach, ncd and klp3A were shown to require only the centromeric region of the chromosome for their roles in chromosome segregation. Increased gene dosage also affected minichromosome transmission and was used to demonstrate that the nod kinesin-like protein gene interacts genetically with the centro mere, in addition to interacting with extracentromeric regions as demonstrated previously. The results presented in this study strongly suggest that dominant genetic interactions between mutations and centromere-defective minichromosomes could be used effectively to identify novel genes necessary for centromere function.     

Spread of HIV infection in married monogamous women in India

CONTEXT: A high prevalence of human immunodeficiency virus (HIV) infection in female sex workers (FSWs) and men who attend sexually transmitted disease (STD) clinics poses a risk for spread of infection to other populations. OBJECTIVE: To examine spread of HIV to a low-risk population by comparing prevalence of, and risk factors for, HIV and STDs in FSWs and non-FSWs. METHODS: Women attending STD clinics in Pune, India, were assessed for STDs and HIV from May 13, 1993, to July 11, 1996. Demographic and behavioral information was collected, and clinical and laboratory assessment was performed. MAIN OUTCOME MEASURE: Prevalence and risk determinants of HIV infection. RESULTS: Of 916 women enrolled, 525 were FSWs and 391 were non-FSWs. Prevalence of HIV in FSWs and non-FSWs was 49.9% and 13.6%, respectively (P<.001). In multivariate analysis, inconsistent condom use and genital ulcer disease or genital warts were associated with prevalent HIV in FSWs. History of sexual contact with a partner with an STD was associated with HIV in non-FSWs. CONCLUSIONS: Infection with HIV is increasing in non-FSWs, previously thought to be at low risk in India. Since history of sexual contact with their only sex partner was the only risk factor significantly associated with HIV infection, it is likely that these women are being infected by their spouses. This underscores the need for strengthening partner-notification strategies and counseling facilities in India.     

Efficacy and safety of a new hydroxymethylglutaryl-coenzyme A reductase inhibitor, atorvastatin, in patients with combined hyperlipidemia: comparison with fenofibrate

This 24-week, randomized, open-label multicenter study evaluated the efficacy and safety of atorvastatin compared with fenofibrate in the treatment of patients with combined hyperlipidemia (CHL). Following a 6-week baseline period, 84 patients with CHL were randomly assigned to either atorvastatin treatment, 10 mg QD for 12 weeks increasing to 20 mg QD for 12 weeks, or fenofibrate treatment, 100 mg TID for 24 weeks. Changes from baseline in lipid parameters were evaluated at weeks 12 and 24. At both 10- and 20-mg doses, atorvastatin treatment resulted in significantly greater reductions in LDL cholesterol, apolipoprotein (apo) B, total cholesterol, LDL-apoB, and lipoprotein-B compared to 300-mg fenofibrate treatment (P < .05). While atorvastatin also resulted in clinically significant reductions in triglyceride, VLDL cholesterol, apoB in VLDL, triglyceride in VLDL, and apoC-III and significant increases in HDL cholesterol and apoA-I levels, fenofibrate was more effective than atorvastatin in altering all these parameters. However, by significantly affecting both the cholesterol-rich and triglyceride-rich particles, atorvastatin holds promise as a lipid-regulator able to adequately treat a broad range of patients that includes those with CHL.     

Transurethral thermotherapy of the prostate--a very promising treatment method for benign prostatic hyperplasia

Transurethral resection of the prostate remains the most common method for the treatment of benign prostatic hyperplasia (BPH). Due to unsatisfactory results in about 18% of the patients new methods to treat BPH have been developed. We evaluated 45 patients 6 and 12 months after transurethral microwave thermotherapy using the Prostatron device with Prostasoft 2.5 software. There was a significant improvement of the urinary symptoms and of the quality of life index from 18 to 9.5 and from 3.2 to 1.6 points, respectively. Urinary flow rate improved from 8.8 to 12.1 ml/sec and residual urine was reduced from 101 to 52 ml. The treatment was well tolerated and side effects were minimal. High-energy transurethral microwave thermotherapy is an effective and safe minimal invasive alternative to treat BPH in selected patients. As no anesthesia is required transurethral microwave thermotherapy can also be offered to high risk and elderly patients.     

Role of cAMP in upregulation of insulin secretion during the adaptation of islets of Langerhans to pregnancy

Islets undergo a number of upregulatory changes to meet the increased demand for insulin during pregnancy, including an increase in glucose-stimulated insulin secretion with a reduction in the stimulation threshold. Treatment with the lactogenic hormone prolactin (PRL) in vitro has been shown to induce changes in islets similar to those observed during pregnancy. We examined cAMP production in islets treated with PRL to determine if changes in cAMP are involved in the upregulation of insulin secretion. Insulin secretion and cAMP concentrations were measured from islets in response to a suprathreshold (6.8 mmol/l) or high (16.8 mmol/l) glucose concentration in the presence of the phosphodiesterase inhibitor isobutylmethylxanthine. Insulin secretion increased by 2.1-, 5.0-, and 5.9-fold at the suprathreshold glucose concentration and by 1.6-, 2.3-, and 2.9-fold at the higher glucose concentration after 1, 3, and 5 days of PRL treatment, respectively. After a similar pattern, cAMP metabolism increased by 1.2-, 1.6-, and 2.1-fold at the suprathreshold glucose concentration and by 1.2-, 1.7-, and 2.2-fold at the high glucose concentration after 1, 3, and 5 days of PRL treatment, respectively. The similar increases in insulin secretion and cAMP concentration suggest that changes in cAMP metabolism are involved in lactogen-induced upregulation of insulin secretion. To gain additional insight into the role of cAMP in the upregulation of islet function after lactogen treatment, we examined the relationship between changes in cAMP concentration and insulin secretion. Under all conditions (differing glucose concentrations and time periods), the increase in insulin release was directly proportional to the increase in cAMP. Thus increased glucose-stimulated insulin secretion from lactogen-treated islets could be accounted for by increased generation of cAMP and did not appear to require any further specific changes in intracellular processes mediated by cAMP. Because the PRL receptor is not directly involved in cAMP metabolism, the lactogen-induced increase in cAMP was most likely due to the increase in glucose metabolism that we have previously demonstrated in PRL-treated islets and in islets during pregnancy.     

Molecular cloning and characterization of a novel form of neuropeptide gene as a developmentally regulated molecule

To examine the molecular basis controlling neuronal differentiation, subtraction library construction and differential screening were used to identify cDNAs whose mRNA levels are regulated in mouse NS20Y cells by dibutyryl cyclic AMP treatment. One of them, N27K, whose mRNA increases transiently during both neuronal differentiation in NS20Y cells and development in mouse brain. The deduced amino acid sequence of N27K comprises 212 amino acid residues and is a novel form of a precursor protein for a new neuropeptide nociceptin/orphanin FQ, which we independently cloned as N23K. That is, the putative protein encoded by N27K is 25 amino acids longer than that encoded by N23K. Using an antibody against a C-terminal peptide of the N27K protein that recognizes a 27-kDa protein in Western blot analysis, a punctate structure in the perinuclear region and areas near the tip of neurites is visualized in neurally differentiating NS20Y cells. The time of maximal expression correlates with periods of neurite extension, and expression decreases as the neuritic network develops. Immunohistochemistry of tissue sections of the mouse central nervous system revealed that reactivity for the anti-N27K protein antibody can detected in early generated neurons at embryonic day 14, in virtually all immature neurons at postnatal day 1, and in subsets of neurons of discrete brain regions such as the hypothalamus and spinal cord in adults. This remarkable redistribution suggests that N27K may be involved in a process in neurite outgrowth and nervous system development.