Advanced primary breast cancer: assessment at mammography of response to induction chemotherapy

The response to induction chemotherapy is an important prognostic factor in patients with nonmetastatic, locally advanced breast carcinomas. Assessment at mammography of the response of 60 breast cancers in 59 women was performed between 1974 and 1986. Responses were excellent in 13 tumors, moderate in 34, and poor in 13 (excellent moderate = 78%). Assessment of response of discrete masses in a fatty breast was easiest; assessment of response of tumor areas that were poorly defined-such as a focal area of architectural distortion or mass in dense breast parenchyma-was more difficult. Of 17 patients with excellent pathologic responses-that is, minimal or no residual tumor-15 (88%) had complete responses (no residual tumor) as determined with mammography, physical examination, or both. Mammography provides information complementary to physical examination and is essential in the accurate assessment of the response to chemotherapy of locally advanced breast cancer.     

Simultaneous acquisition of emission and transmission data for improved thallium-201 cardiac SPECT imaging using a technetium-99m transmission source.

Transmission computed tomography (TCT) data provides useful complementary information to single-photon emission computed tomography (SPECT) reconstructions, especially for cardiac studies. In particular, TCT data has been used to correct for nonuniform attenuation in the chest. Typically the transmission data are acquired in a separate acquisition, but simultaneous acquisition is preferable both to save time and to avoid difficulties involved with registration. In this work, we present a technique for simultaneously acquiring 201Tl SPECT and TCT data using a 99mTc sheet source that requires only minor equipment modifications. The use of these isotopes results in cross-contamination of the emission and transmission data. We present a practical technique to compensate for this contamination using post-acquisition image processing. This technique was evaluated by performing phantom and patient studies. The resulting images compare well with data obtained from separate emission and transmission studies.     

Hematologic disorders in pregnancy.

Hematologic disorders in pregnancy are relatively common and encompass a wide spectrum of clinical conditions. The treatment and obstetric management of the majority of these diseases are well established, although controversy exists in areas such as sickle cell disease and ITP. Once the diagnosis of a specific disorder is confirmed, therapy is directed toward improved perinatal outcome. Recent advances in prenatal diagnostic techniques make in utero diagnosis feasible for most of the inherited disorders and aid in genetic counseling.     

Soemmering's ring support for posterior chamber intraocular lens implantation during penetrating keratoplasty. Changing trends in bullous keratopathy.

BACKGROUND: Changing trends in cataract extractions have resulted in a new category of bullous keratopathy: corneal decompensation after complicated extracapsular cataract extraction. These cases of bullous keratopathy are associated with rupture of the posterior capsule, vitreous loss, and significant intraocular inflammation at the time of the original complicated extracapsular cataract extraction. METHODS: The authors reviewed 14 consecutive cases of penetrating keratoplasty for bullous keratopathy in which posterior chamber intraocular lens implantation was supported by remnants of the posterior capsule and/or Soemmering's ring without suture fixation. All 14 patients had a history of complicated extracapsular cataract extraction with capsule rupture and vitreous loss. RESULTS: All 14 patients had clear, compact grafts without migration of the intraocular lens with a mean follow-up of 12.1 months. Vision improved in 93% of cases, and there was no significant worsening of glaucoma. CONCLUSIONS: Pseudophakic bullous keratopathy after traumatic extracapsular cataract extraction with an anterior chamber intraocular lens and aphakic bullous keratopathy after traumatic extracapsular cataract extraction are two relatively new clinical entities that present new intraocular lens management options. Bullous keratopathy after complicated extracapsular cataract extraction should be recognized as a distinct clinical entity. Intraocular lens implantation into the ciliary sulcus with Soemmering's ring and peripheral capsular support provide the advantages of a posterior chamber intraocular lens without the risk of iris or scleral sutures. The authors predict that bullous keratopathy associated with traumatic extracapsular cataract extraction will become one of the more common indications for penetrating keratoplasty.     

The acute inflammatory response to lipopolysaccharide in CNS parenchyma differs from that in other body tissues.

Acute inflammation is important for defence against infection, wound repair and the mediation of auto-immune tissue destruction. Myelomonocytic recruitment in acute inflammation is a stereotyped and non-specific response to tissue insult which begins within 2 h. In this study, lipopolysaccharide was injected into the murine CNS and other body sites of mice to compare the inflammatory responses. Doses of lipopolysaccharide which induced typical myelomonocytic recruitment in skin and the choroid plexus had no effect in CNS parenchyma, apart from the morphological activation of local resident microglia. The CNS parenchymal response proceeded independently of that in the choroid plexus-cerebral ventricles and had three distinct and unique phases. Initially there was minimal neutrophil exudation and a two-day delay before any increase in macrophage-microglial cell number. Next, there was a rapid increase in macrophage-microglial cell numbers during the third day, mainly due to recruitment of blood monocytes. During this phase, leukocyte recruitment was restricted to monocytes which rapidly adopted the arborized microglial phenotype. Monocytes migrated through an intact blood-brain barrier independent of changes in solute permeability. Finally, there was a florid myelomonocytic reaction predominantly in the white matter, one week after intracerebral injection of 2 micrograms lipopolysaccharide. At this time, the leukocyte reaction disrupted the blood-brain barrier, mononuclear phagocytes expressed macrophage morphology and abundant major histocompatibility complex Class II antigen, and T lymphocytes were present. Myelomonocytic entry into the CNS was partially inhibited by prior blockade of the type 3 complement receptor, known to mediate leukocyte adhesion to endothelium elsewhere. The processes which lead to rapid myelomonocytic recruitment in other tissues are absent in CNS parenchyma. Understanding the molecular mechanisms responsible could have considerable significance both for CNS pathophysiology as well as possible anti-inflammatory therapeutic application elsewhere in the body.     

GGA1 acts as a spatial switch altering amyloid precursor protein trafficking and processing

The beta-amyloid (Abeta) precursor protein (APP) is cleaved sequentially by beta-site of APP-cleaving enzyme (BACE) and gamma-secretase to release the Abeta peptides that accumulate in plaques in Alzheimer's disease (AD). GGA1, a member of the Golgi-localized gamma-ear-containing ARF-binding (GGA) protein family, interacts with BACE and influences its subcellular distribution. We now report that overexpression of GGA1 in cells increased the APP C-terminal fragment resulting from beta-cleavage but surprisingly reduced Abeta. GGA1 confined APP to the Golgi, in which fluorescence resonance energy transfer analyses suggest that the proteins come into close proximity. GGA1 blunted only APP but not notch intracellular domain release. These results suggest that GGA1 prevented APP beta-cleavage products from becoming substrates for gamma-secretase. Direct binding of GGA1 to BACE was not required for these effects, but the integrity of the GAT (GGA1 and TOM) domain of GGA1 was. GGA1 may act as a specific spatial switch influencing APP trafficking and processing, so that APP-GGA1 interactions may have pathophysiological relevance in AD.     

Sensitive trace-first liquid chromatographic determination of 4-aminopyridine in 3,4-diaminopyridine

For the treatment of human neuromuscular diseases, 3,4-diaminopyridine (DAP) is six to ten times more effective than 4-aminopyridine (AP), but only half as convulsant and toxic. Therefore, there is a need for the determination of AP in DAP. With only conventional equipment, high-pressure liquid chromatography can be used for the extremely sensitive detection of a trace contaminant under one condition: that is, the trace must be eluted before the major component it contaminates. Prior elution presents a trace peak in a fully exploitable form that is maximally efficient and maximally observable. This has already been demonstrated with a Pirkle-concept chiral stationary phase for determination of a chiral trace. However, its application to determination of a nonchiral trace with a reversed phase has not previously been reported. Such an application is reported here. In this demonstrative study, selectivity and loading capability were iteratively improved. Ion pairing with dodecanesulfonate maximized selectivity. It was again shown that using a less concentrated sample in greater volume maximizes loading capability without obscuring the peak of the trace. Eventually, the ability to detect 0.005% AP in DAP was demonstrated. Whether that sensitivity might be improved still more, perhaps with a larger column, was not established.     

Glued-on, rigid gas-permeable contact lens for severe radiation-induced keratitis.

A 68-year-old woman with severe radiation-induced keratoconjunctivitis sicca became progressively unresponsive to conventional medical treatment. Her left eye deteriorated rapidly and required total tarsorrhaphy. In an attempt to stabilize the right eye and preserve some functional vision, we glued a high-Dk rigid, gas-permeable contact lens with tissue-grade cyanoacrylate adhesive to Bowman's membrane. This glued-on contact lens induced rapid and dramatic improvement of the patient's comfort and sight. Recent developments in high-permeability, rigid, contact-lens materials now make artificial replacement of the epithelium a potentially useful treatment for severe ocular surface disease when conventional treatment has failed.