Ultrasound Densitometric Analysis: Comparison Between an Online Digital Acquisition Acoustic Program and an Offline Analog Program

Videodensitometric analysis of myocardial contrast echocardiography is traditionally performed off line. Recently, an online contrast ultrasound analysis system, Acoustic Densitometry (Hewlett-Packard), was introduced. We compared pixel intensities acquired with Acoustic Densitometry to pixel intensities derived from videodensitometry. A tissue phantom was imaged in phase I using three transducer frequencies (2.5, 3.5, and 5.0 MHz). In phase II, an in vitro flowing tube model with various concentrations of Albunex® was imaged at two flow rates, 0.6 and 1.2 m/sec, and at two transducer frequencies, 2.5 and 3.5 MHz. The relationship between pixel intensities yielded by the two systems for identical ultrasound signals was determined with linear regression. Intensities derived with Acoustic Densitometry strongly correlated with those derived from the offline videodensitometry system. The intensities were related by a predictive multiplicative factor based on display characteristics of the two systems. These results suggest that semiquantitative, online perfusion analysis with Acoustic Densitometry is as sensitive as analysis offline with videodensitometry.     

Chemotherapy for desmoid tumours in association with familial adenomatous polyposis: a report of three cases

Objective

To determine the efficacy of chemotherapy for inoperable desmoid tumours associated with familial adenomatous polyposis.

Design

A review of three cases of unresectable desmoid tumours and of the literature on the subject.

Setting

The Steven Atanas Stavro Polyposis Registry at Mount Sinai Hospital in Toronto.

Patients

Three patients with symptomatic, unresectable desmoid tumours associated with familial adenomatous polyposis and unresponsive to conventional hormone therapy.

Intervention

A chemotherapy regimen of seven cycles of doxorubicin (dose ranging from 60 to 90 mg/m²) and dacarbazine (1000 mg/m²), followed by carboplatin (400 mg/m²) and dacarbazine.

Outcome Measures

Clinical improvement and tumour regression demonstrated by computed tomography.

Results

In each of the three cases significant tumour regression was seen clinically and radiologically.

Conclusions

Cytotoxic chemotherapy is an effective treatment for desmoid tumours associated with familial adenomatous polyposis. The chemotherapy should be started early in cases of symptomatic desmoid tumour unresponsive to conventional medical therapy.     

Comparison of fascial and vaginal wall slings in the management of intrinsic sphincter deficiency

Objectives

To compare safety and efficacy of fascial versus vaginal wall slings in the management of women with intrinsic sphincter deficiency (ISD).

Methods

The hospital and office records of 79 consecutive women with ISD were retrospectively analyzed from January 1991 to September 1995. There were 43 fascial slings (group A) and 36 vaginal wall slings (group B). Parameter of evaluation included efficacy based on postoperative presence of stress or urge incontinence and number of pads used, complications, and miscellaneous factors, including length of catheterization time, length of hospitalization, quantity of analgesics used, and loss of work days.

Results

Baseline clinical and urodynamic data were the same for both groups. Pad use decreased from 6.9 to 0.6 for group A and from 5.7 to 0.3 for group B. Persistent stress and urge incontinence was present in 5% and 16% of group A patients and in 3% and 11 % of group B patients, respectively. Group A (89%) and group B (94%) patients were either very satisfied or satisfied with their surgical outcome. The operative time, hospital days, and days lost from work for group B patients (42.3 ± 13.4 minutes, 1.4 ± 0.9 days, 18.4 ±3.2 days, respectively) were significantly lower than for group A patients (84.2 ± 17.8 minutes, 3.7 ± 1.9 days, 28.4 ±7.8 days, respectively).

Conclusions

Both fascial and vaginal wall slings are effective in treating women with ISD. However, the use of vaginal wall slings resulted in significantly shorter hospital stay, decreased catheterization time, decreased use of analgesics, and decreased loss of days of work compared with fascial slings. Therefore, the vaginal wall sling should be the preferred surgical method of treating intrinsic sphincter deficiency.     

Catecholamines modulate growth and differentiation of human preosteoclastic cells

Using a clonal cell line of human osteoclast precursors (FLG 29.1 cells), that after treatment with 12-O-tetradecanoyl phorbol 13-acetate (TPA) show many functional characteristics of osteoclasts, we demonstrated that catecholamines act as inducers of osteoclast maturation in vitro and as stimulators of osteoclast activity via the binding to ₂ adrenergic receptors. Scatchard analysis of¹²⁵I-labelled iodocyano-pindolol to untreated (undifferentiated) or TPA-treated (differentiated) FLG 29.1 cells revealed the presence of a single high-affinity site with aK _d value around 24 pM and 8 pM respectively and with superimposable binding capacity (1.18 fmol/mg protein). Catecholamines increased in a dose-dependent fashion the intracellular cyclic AMP (cAMP) accumulation in both undifferentiated and TPA-treated FLG 29.1 cells. Pretreatment of untreated and TPA-treated FLG 29.1 cells with propranolol inhibited the catecholamine effect on cAMP accumulation, while pretreatment with clonidine had no effect. Catecholamines also reduced cell proliferation, increased tartrate-resistant acid phosphatase (TRAcP) activity, interleukin 6 (IL-6) production, multinuclearity and response to salmon calcitonin (sCT) in undifferentiated FLG 29.1 cells. In differentiated FLG 29.1 cells only IL-6 release was induced by catecholamine treatment. These findings support a potential role for catecholamines in modulating osteoclast differentiation and mature osteoclast activity.     

Pay Status as a Predictor of Outcome in Surgical Treatment of Obesity

Background: Higher complication rates and lower success in surgery for severe obesity have been reported for patients with government pay status. We examined the effect of pay status upon outcome in surgical treatment of obesity. Methods: This was an observational study from an aggregate data set of individual patient information. Government pay status (G) was defined as full or partial medical care payment through Medicare, Medicaid, or Veterans Administration. Payment entirely by private insurance was defined as private (P). Operations were classified as either simple (S, gastric restriction) or complex (C, gastric restriction with small bowel bypass). Two measures of outcome, perioperative complication rate and weight loss success (≤50% excess weight), were examined to determine pay status effect. Results: More G than P patients were treated with simple procedures (79% vs 51%, p < 0.05). Perioperative complication rates were more common for G than P patients (14.4% vs 9.1%, p < 0.05). One-year weight loss success was higher for P than G, regardless of operation type. Conclusion: Pay status should be included in characterization of patient groups and in the analysis of results when effectiveness of surgical treatment for severe obesity is reported.     

Comparative Pharmacology of Cisatracurium (51W89), Atracurium, and Five Isomers in Cats

Background: Atracurium has four chiral centers and the marketed product is a mixture of ten optical and geometric isomers. Six of the isomers were prepared and evaluated for neuromuscular blocking activity and autonomic effects in anesthetized cats. This study reports the comparative pharmacology of the six isomers and atracurium that led to the selection of one isomer, cisatracurium (Nimbex, 51W89) for clinical development.

Methods: Purpose bred cats, anesthetized with alpha-chloralose (80 mg/kg) and pentobarbital sodium (7 mg/kg) administered intraperitoneally, were used in this study. Neuromuscular blocking effects were assessed from the effects on the tibialis anterior twitch evoked at 0.15 Hz. Inhibition of the autonomic nervous system was assessed from the effects on the nictitating membrane contraction, in response to preganglionic sympathetic nerve stimulation and the bradycardia/vasodepressor responses to vagal nerve stimulation. Cardiovascular effects and plasma histamine concentrations were determined after a bolus injection of cisatracurium or atracurium.

Results: Like atracurium, all six isomers produced dose-dependent neuromuscular block (NMB). The calculated ED95 NMB values varied approximately tenfold (43+/-2 micro gram/kg-488+/-56 micro gram/kg). The "R-series" isomers were more potent than the corresponding "S series" isomers. With the exception of the S,Trans-S', Trans isomer, the NMB effects, i.e., onset times (range 2.6+/-0.2 min to 4.7+/-0.3 min) and total durations (range 9.9+/- 1.4 min to 14+/-0.9 min), of the other five isomers were very similar to that of atracurium. The former isomer had a relatively short duration of action. The 25-75% recovery times after cisatracurium at 1x ED sub 95 (4.4+/-0.4 min), 4x ED95 (4.5+/-0.4 min), and continuous infusions lasting at least 60 min that maintained 95-99% NMB (4.8+/-0.4 min) indicated a noncumulative effect. The vagal ID50: NMB ED95 ratios for atracurium and the six isomers ranged from 2 to 27. The sympathetic ID25: NMB ED95 ranged from 2.7 to 60. Atracurium and all of the isomers, except cisatracurium, produced cardiovascular effects after intravenous bolus administration at large doses (700-4,800 micro gram/kg). In contrast to atracurium, there were no changes in plasma histamine concentrations associated with the administration of doses of cisatracurium equivalent to 60x the NMB ED95 (62+/-8 micro gram/kg).     

Back to the future for wound care?

The European Renaissance was a time of enormous change and rapid progress in the arts, sciences, and medicine. A glimpse of wound care in the last phase of the European Renaissance is provided by the analysis of work by Wilhelm Fabry, the "father of German surgery," as provided in his book De Combustionibus ("Burns") which details his range of treatments for the burn wound, as well as his approach to the later problems of scarring and contracture. We describe some of the historic events which may have stimulated Fabry's writings, in particular, the influences passed down from the medical school of Padua which thereby advanced the cause of wound care and surgery. Finally, we briefly explore the potential of such an approach to the works of our medical forefathers.     

Molecular diagnosis of exocrine pancreatic cancer using a percutaneous technique

Background: The K-ras oncogene is activated by point mutations at codon 12 in most patients with exocrine pancreatic cancer. Mutant-enriched polymerase chain reaction (PCR) amplification can enhance the detection of mutated K-ras. This technique was applied to patients undergoing percutaneous fine-needle aspiration (FNA) biopsy of suspect pancreatic lesions. Methods: Twenty-five patients underwent percutaneous FNA of the pancreas for cytologic and molecular analysis. After preparing cytologic smears, the 22-gauge needle and syringe used for FNA were rinsed in RPMI-1640. The specimen was centrifuged, and DNA was extracted from the supernatant and subjected to mutant-enriched PCR using appropriate mismatched primers that introduce a BstNI restriction endonuclease cleavage site at codon 12 of wild-type, but not mutant, K-ras. After digestion with BstNI, the DNA was reamplified. To increase assay sensitivity, the final five PCR cycles were completed incorporating 5 μCi of (α-32P)dCTP. The DNA was then redigested and subjected to gel electrophoresis and autoradiography. Results: The median amount of DNA retrieved per specimen was 3.33 μg. Mutant K-ras was detected as a band of 143 bps; residual wild-type DNA was seen as a 114-bp fragment. Twenty-one of 25 specimens demonstrated mutated K-ras DNA. Two patients with nondiagnostic cytology results had mutated K-ras DNA; adenocarcinoma of pancreatic origin was confirmed in both cases after pancreatectomy. Conclusion: The molecular diagnosis of pancreatic cancer through identification of mutations in K-ras can be readily performed on specimens obtained by percutaneous FNA. As aggressive multimodality management of this disease becomes more common, pretreatment analysis of molecular determinants may have greater clinical significance. Presented at the 48th Cancer Symposium of The Society of Surgical Oncology, Boston, Massachusetts, March 23–26, 1995.     

Role of endogenous interferon gamma in murine tumor growth and tumor necrosis factor alpha antitumor efficacy

Background: The anticancer role of tumor necrosis factor-alpha (TNF-) has been limited by toxicity. These experiments evaluate blocking endogenous interferon-gamma (IFN-) activity to abrogate TNF- toxicity. Methods: C57Bl/6 mice bearing MCA 105 tumor were treated with TNF- and anti-IFN- antibody (Ab) to evaluate the effect on the acute lethality of TNF- and their efficacy as evaluated by tumor growth rate, tumor histology, and survival. Results: Anti-IFN- Ab decreased TNF- lethality. Anti-IFN- Ab alone increased tumor growth significantly more than did nonimmune IgG (p₂<0.0001). Tumor-bearing mice that received nonimmune IgG and TNF- had slower tumor growth (p₂<0.02) and a trend toward improved survival (p=0.07) compared with saline-treated controls. Anti-IFN- Ab abrogated the antitumor effect of TNF-, prevented acute tumor necrosis histologically, and resulted in tumor growth rate and host survival similar to that of controls. The findings in mice that received anti-IFN- Ab and high-dose TNF- were comparable with those in mice that received a lower, equitoxic dose of TNF- alone. Conclusions: Blocking endogenous IFN- accelerates tumor growth in this model and partially abrogates the toxic and antitumor activity of exogenous TNF- equally. This suggests that blocking endogenous IFN- activity is not a useful strategy for limiting TNF- treatment toxicity.Presented in part at the 45th Annual Cancer Symposium of The Society of Surgical Oncology, New York, New York, March 15–18, 1992.