Cardiac management during adjuvant trastuzumab therapy: recommendations of the Canadian Trastuzumab Working Group.

Trastuzumab has been shown to be an effective therapy for women with breast cancer that overexpresses the human epidermal growth factor receptor 2 (her2) protein. In the pivotal metastatic breast cancer trials, cardiac dysfunction was observed in women treated with trastuzumab and chemotherapy. The incidence and severity of cardiac dysfunction was greatest among patients who received trastuzumab in combination with anthracycline-based therapy. Those findings influenced the design of subsequent trastuzumab trials to include prospective evaluations of cardiac effects and protocols for cardiac monitoring and management. The risk of cardiotoxicity has also driven efforts to develop non-anthracycline-based regimens for women with her2-positive breast cancers.With the increasing use of trastuzumab, particularly in the curative adjuvant setting, the need for a rational approach to the treatment and cardiac management of the relevant patient population is clear. The mandate of the Canadian Trastuzumab Working Group was to formulate recommendations, based on available data, for the assessment and management of cardiac complications during adjuvant trastuzumab therapy. The panel formulated recommendations in four areas: Risk factors for cardiotoxicity, Effects of various regimens, Monitoring, Management. The recommendations published here are expected to evolve as more data become available and experience with trastuzumab in the adjuvant setting grows.

Expression of cell surface transmembrane carbonic anhydrase genes CA9 and CA12 in the human eye: overexpression of CA12 (CAXII) in glaucoma.

PURPOSE: Carbonic anhydrase enzymes (CAs) are universally involved in many fundamental physiological processes, including acid base regulation and fluid formation and movement. In glaucoma patients, CA inhibitors are very effective in lowering intraocular pressure by reducing the rate of aqueous humour secretion mediated by the CAs in the ciliary epithelium. In this work, we investigated the expression and tissue distribution of two recently discovered CA genes CA9 (CAIX) and CA12 (CAXII) in fetal, neonatal, and adult human eyes with and without glaucoma. METHODS: CAIX and CAXII expression in 16 normal and 10 glaucomatous eyes, and in cultured non-pigmented ciliary epithelial cells (NPE) from normal and glaucoma eye donors was assessed by immunostaining. In addition, northern blot hybridisation was performed to assess expression of CA4, CA9, and CA12 mRNA in cultured NPE cells from normal and glaucoma donors. RESULTS: CAXII was localised primarily to the NPE with its expression prominent during embryonic eye development but which decreased significantly in adults. CAIX expression in the NPE was very low. The epithelium of cornea and lens occasionally expressed both enzymes at low levels during development and in adult eye, and no expression was detected in the retina. The NPE from glaucoma eyes expressed higher levels of CAXII, but not CAIX, in comparison with normal eyes. This expression pattern was retained in cultured NPE cell lines. NPE cells from a glaucoma patient showed a five-fold increase in the CA12 mRNA level with no detectable expression of CA9 mRNA. Also, no expression of the CA4 gene encoding a GPI anchored plasma membrane protein was detected on these northern blots. CONCLUSIONS: Transmembrane CAIX and CAXII enzymes are expressed in the ciliary cells and, thus, may be involved in aqueous humour production. CA12 may be a targeted gene in glaucoma.

Parents' attitudes, knowledge, and behavior toward youth gambling: a five-year follow-up.

This study compares the attitudes, knowledge, and behavior of parents of 5- to 17-year-old children regarding youth gambling. This information was obtained through two telephone surveys conducted in 1995, and 5 years later in 2000, in the Québec City area. Survey 1, in 1995, was conducted on 279 respondents, while survey 2, in 2000, was carried out with 213 respondents. Results showed a number of changes in parents' attitudes, behavior, and knowledge concerning youth gambling: For example, parents' perception of the age of onset of gambling behavior had improved slightly at the end of the 5-year period. Furthermore, parents were more satisfied with government limitation of access to gambling, and more accurately informed about legal aspects of the sale of lottery tickets. However, the percentage of parents who failed to associate youth gambling with some of its correlates (arcade attendance, parental gambling problems, and friendship with gamblers) increased from 1995 to year 2000. The improvements that were observed suggested that parents had benefited from media-transmitted information during this period. However, the deterioration of some parental attitudes, and the stability of other variables, suggest that it is still important to educate parents about youth gambling, and to design interventions adapted to parents' needs.

Extensive lower eyelid pigment spread after blepharopigmentation.

PURPOSE: To report on a complication of blepharopigmentation. METHODS: Case report. RESULTS: An 81-year-old woman underwent cosmetic tattooing of all four eyelids. The pigment immediately spread from the right lower eyelid lash line to the nasojugal fold. The dispersion was so extensive in surface area that nonsurgical techniques for ameliorating the dispersion would not be effective. The unintentionally tattooed skin was excised and reconstructed with a lateral canthal suspension and full thickness skin grafts. Pathologic examination of the excised tissue revealed pigmentation of all layers of the skin and the surface of the orbicularis muscle. CONCLUSION: This case illustrates that extensive pigment spread following blepharopigmentation may require extensive reconstruction to correct the problem.

Keratohematoma leading to acquired posterior keratoconus.

We describe a patient with congenital syphilis associated with corneal neovascularization and subsequent intracorneal hemorrhage. Over time, this condition resulted in acquired posterior keratoconus. A review of our clinical case, the literature, and histologic findings is presented. To our knowledge, this is the first reported case of acquired posterior keratoconus associated with corneal vascularization and hemorrhage secondary to congenital syphilis. We also have provided histopathologic evidence for the prescence of an iron ring.

The role of histopathology in the diagnosis and management of uveitis.

Intraocular inflammation/uveitis is one of the more poorly understood areas in the field of ophthalmology. We hope to improve this understanding by first reviewing the classic histopathologic approach to intraocular inflammation, and then by integrating that with the current role of histopathology in the diagnosis and management of uveitis. Herein, we will present a systematic approach, beginning with the most accessible conjunctival, lacrimal gland and lymph node biopsy sites; extending through anterior chamber tap, iris biopsy, and vitrectomy and ending with retinal or chorioretinal biopsy of distant organ sites. We will show how a combination of these histopathologic elements can aid in the diagnosis, and thereby the management, of intraocular inflammations and uveitis.

A single-blind study of pulse oximetry in children.

Oxygen saturation determined by pulse oximetry was monitored in 152 pediatric surgical patients divided into two groups. In one group, the oximeter data and alarms were available (N = 76) to the anesthesia team, and, in the other group, these data were unavailable (N = 76). A trained observer recorded all intraoperative hypoxic episodes and informed the anesthesia team of all major events (i.e., oxygen saturation less than or equal to 85% for greater than or equal to 30 s) (PaO2 approximately 52 mmHg). Thirty-five major events occurred: 24 in the unavailable group, and 11 in the available group (P = 0.021). A greater number of major events occurred in children less than or equal to 2 yr of age (P = 0.013). Hypoxic events diagnosed by the oximeter, but not by the anesthesiologist, were more frequent in the unavailable group (13) than in the available group (5) (P = 0.0495). ASA Physical Status 3 and 4 patients were more likely to suffer a major event (P = 0.009 available, 0.006 unavailable). The pulse oximeter diagnosed hypoxemia before the signs and symptoms of hypoxemia were apparent (i.e., prior to observed cyanosis or bradycardia). Major hypoxic events were unrelated to duration of anesthesia. Major events were evenly distributed among induction, maintenance, and awakening from anesthesia; a greater number of hypoxic events occurred during induction in the unavailable group (P = 0.031). No morbidity was documented in any patient who suffered an hypoxic event.(ABSTRACT TRUNCATED AT 250 WORDS)

Depressant effect on the retrograde atrioventricular nodal conduction of beta-adrenergic blockade by propranolol in humans.

Propranolol is known to have a depressant effect on anterograde atrioventricular (AV) nodal conduction in normal subjects and in those with AV nodal reentrant tachycardia. Using His bundle recording and programmed ventricular stimulation, the effect of propranolol-induced beta-adrenergic blockade (1 mg/kg intravenously) on retrograde AV nodal conduction was studied in 17 patients without (group I) and nine with (group II) AV nodal reentrant tachycardia. During baseline studies the ventricular pacing cycle length that induced ventriculoatrial block was 338 +/- 60 ms (range 260 to 450 ms) in group I and 305 +/- 39 ms (range 260 to 375 ms) in group II patients (not significant). After injection of propranolol, the ventricular pacing cycle length that induced ventriculoatrial block in group I patients was 416 +/- 97 ms (range 300 to 550 ms) (P less than 0.001, compared to baseline state) in 15 patients, and complete block occurred in two patients. In group II patients ventriculoatrial block occurred at a ventricular pacing cycle length of 375 +/- 97 ms (range 260 to 510 ms) (P less than 0.02 compared to baseline value) in eight patients, and complete block occurred in one patient. Retrograde AV nodal conduction expressed as the H2A2 interval was 75 +/- 33 ms (range 35 to 150 ms) in group I and 49 +/- 16 ms (range 20 to 80 ms) in group II patients (P less than 0.05). Following the administration of propranolol, the H2A2 interval was prolonged in group I patients by 10 to 45 ms in 11 patients, no retrograde AV nodal conduction was observed in three patients, and there was no effect in two patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Heinz-body anemia due to severe cresol poisoning: successful treatment with erythrocytapheresis.

A patient with massive intravascular Heinz-body hemolytic anemia associated with the presence of bizarre-looking erythrocytes following the oral ingestion of approximately 100 mL of "penetrating oil", a petroleum distillate containing 85% kerosene, 12% cresol and 2% surfactant, is described. He was treated successfully with immediate erythrocytapheresis and forced diuresis.