The influence of diabetes on free flap transfer: I. Flap survival and microvascular healing.

Although recent clinical case presentations suggest that diabetes does not predispose free tissue transfers to increased risk of failure, this remains an open question. The present study used a syngeneic rat strain (Lewis) for free groin flap transplantations between normal rats and streptozotocin-induced diabetic rats (2 months' duration of symptoms), to investigate the influence of diabetes on flap transfer. Flap survival at 1 week, vascular patency, flap histology and ultrastructure, and scanning electron microscopy of anastomotic sites and of corrosion casts of flap vasculature were used as bases for comparison. No differences were found in comparisons of flap survival between any groups of transfer combinations (normal flap onto normal recipient, diabetic flap onto normal recipient, normal flap onto diabetic recipient, and diabetic flap onto diabetic recipient); 100% success was achieved in each group. No differences were found in histology or corrosion casts. Transmission electron microscopy revealed a thickening of the capillary basement membrane in rat diabetic skin after only 8 weeks of symptoms. This ultrastructural finding is consistent with similar capillary basement membrane thickening seen in many other tissues of short- and long-term diabetic animals and humans. Re-endothelialization across the arterial anastomosis at 2 weeks postoperatively was significantly faster in normal versus diabetic animals (p less than 0.05). The predominantly negative findings of this study support the application of free flap transfers in diabetic patients. It is concluded that reconstructive efforts involving free tissue transfer may not be contraindicated in diabetic patients.     

The solid variant of adenoid cystic carcinoma of the cervix.

We studied seven examples of the solid variant of adenoid cystic carcinoma of the uterine cervix in postmenopausal women who presented with vaginal bleeding and a large ulcerated or polypoid cervical mass. The tumors lacked the characteristic cribriform pattern of conventional adenoid cystic carcinoma. The neoplastic cells were small, undifferentiated, or basaloid and grew in cords, nests, trabeculae, and nodules. Foci of squamous cell carcinoma were seen in three tumors and areas of necrosis in four. A characteristic feature was the production of abundant periodic acid-Schiff's procedure (PAS)-positive basement membrane material that was immunoreactive for collagen IV and that in some areas compressed tumor cells. Electron microscopy on three cases showed globules and cylinders of redundant basal lamina. The tumor cells were joined by desmosomes and contained bundles of tonofilaments. Material similar to basement membrane material appeared to be intracytoplasmic in two tumors. No neurosecretory granules or myoepithelial cells were found. Four deaths were tumor related. Two patients are currently alive, but with local recurrence or metastases; another is alive and well 19 months after surgery. We believe that the solid variant of adenoid cystic carcinoma of the cervix is a distinctive neoplasm that should be separated from small cell carcinomas with or without endocrine features, adenoid basal cell carcinoma, and squamous cell carcinoma.     

Risk factors for acquisition of multiply drug-resistant gram-negative bacteria

Some bacteria are naturally resistant to many antibiotics and most can become multiply resistant. Multiply resistant gram-negative bacteria have proved a particular problem over the last 30 years, but the development of new agents has lessened their significance for most clinicians. Now, however, clinical practice is threatened by the lack of new classes of antibiotics, the widespread emergence of resistance and the advent of plasmid-mediated cephalosporinases by which the spread of resistance is likely to be rapid. Increased use of prophylaxis in immunosuppressed and intensive care patients is likely to aggravate the problem, as is the use of new broad-spectrum agents in the community. More directed and restricted antibiotic use and better education of patients and prescriber are necessary to contain the problem of antibiotic resistance. Improved surveillance of sensitivity trends is essential. Many outbreaks also are associated with poor infection control techniques. The cost of outbreaks due to multiply resistant organisms and lack of compliance with infection control procedures needs to be properly studied. While many predisposing factors for the acquisition of these organisms and the development of infection are understood, the multifactorial nature of illness in many patients complicates the issue, necessitating further study of risk factors and preventative and therapeutic measures.     

Tumor targeting by an aptamer.

Aptamers are small oligonucleotides that are selected to bind tightly and specifically to a target molecule. We sought to determine whether aptamers have potential for in vivo delivery of radioisotopes or cytotoxic agents. METHODS: TTA1, an aptamer to the extracellular matrix protein tenascin-C, was prepared in fluorescent and radiolabeled forms. After in vivo administration, uptake and tumor distribution of Rhodamine Red-X-labeled aptamer was studied by fluorescence microscopy. In glioblastoma (U251) and breast cancer (MDA-MB-435) tumor xenografts, biodistribution and imaging studies were performed using TTA1 radiolabeled with (99m)Tc. Tenascin-C levels and tumor uptake were studied in a variety of additional human tumor xenografts. To assess the effect of radiometal chelate on biodistribution, mercapto-acetyl diglycine (MAG(2)) was compared with diethylenetriaminepentaacetic acid and with MAG(2)-3,400-molecular-weight PEG (PEG(3,400)). RESULTS: Intravenous injection of fluorescent aptamer TTA1 produced bright perivascular fluorescence in a xenografted human tumor within 10 min. In the ensuing 3 h, fluorescence diffused throughout the tumor. Labeled with (99m)Tc, TTA1 displayed rapid blood clearance, a half-life of less than 2 min, and rapid tumor penetration: 6% injected dose (%ID)/g at 10 min. Tumor retention was durable, with 2.7 %ID/g at 60 min and a long-lived phase that stabilized at 1 %ID/g. Rapid tumor uptake and blood clearance yielded a tumor-to-blood ratio of 50 within 3 h. Both renal and hepatic clearance pathways were observed. Using the (99m)Tc-labeled aptamer, images of glioblastoma and breast tumors were obtained by planar scintigraphy. Aptamer uptake, seen in several different human tumors, required the presence of the target protein, human tenascin-C. Modification of the MAG(2) radiometal chelator dramatically altered the uptake and clearance patterns. CONCLUSION: TTA1 is taken up by a variety of solid tumors including breast, glioblastoma, lung, and colon. Rapid uptake by tumors and rapid clearance from the blood and other nontarget tissues enables clear tumor imaging. As synthetic molecules, aptamers are readily modified in a site-specific manner. A variety of aptamer conjugates accumulate in tumors, suggesting imaging and potentially therapeutic applications.     

The pathologist's examination of the "lumpectomy"--the pathologists' view of surgical margins.

Despite the widespread conservative management of breast cancer, the pathologists' examination of these specimens is far from uniform. Pathologists sample margins differently, and even disagree on what constitutes a positive margin. This variability in the pathologic examination of the lumpectomy creates tremendous problems in analyzing the existing literature on the importance of positive margins. Herein is a discussion of the available data on the significance of margin assessment. We furthermore suggest a practical approach to examining margins with an emphasis on a functional orientation of the specimen with respect to the nipple. Only by adopting a uniform system of margin assessment can we begin to critically evaluate the importance of positive margins in segmental resections of the breast.     

The effect of venous flow alterations upon patency of rat femoral vein anastomoses.

The rat femoral vein has become a standard model for laboratory training in microvascular anastomotic technique as well as for research investigations into factors affecting venous patency. This study examined the short-term patency (1 and 7 days) of rat vein anastomoses. The influences upon patency of epigastric flap creation and distal femoral vessel ligation (epigastric flow only) were explored. In a separate experiment, blood flow from the femoral vein was determined through catheter collection of venous efflux; the influences of island epigastric flap creation and distal femoral ligation on flow rates were explored. It was found that 82% of basic femoral vein anastomoses were patent at one day, while 100% of anastomoses associated with an epigastric flap and ligated/transected distal femoral vessel circulation (creating a low-tension anastomosis) were patent (P less than 0.01). With distal femoral vessel ligation and no transection (normal tension at the repair), anastomoses were patent in 90% of the veins when an epigastric flap was also raised, and in 60% when a flap was not created. When a flap was raised without disturbing the distal femoral circulation, vein patency was 75% at one day. When the vein anastomosis was performed with distal femoral vein ligation, the patency rate was 50%. All veins patent at 1 day were also patent at 7 days post-op; 96% of veins clotted at 1 day were found to be patent at 7 days. The venous efflux was not found to vary significantly when an epigastric flap was raised.(ABSTRACT TRUNCATED AT 250 WORDS)