Clinical usefulness of botulinum toxin in the lower extremity

As the literature that pertains to botulinum toxin expands, the scope of treatment options broadens. Although initial uses of botulinum toxin focused around the head and neck, there are many uses for the toxin in the area of the foot and ankle; more possibilities are under investigation every day. We review the uses and techniques for botulinum toxin in the foot and ankle and present results of botulinum toxin treatment in 10 idiopathic toe walkers.     

Effects of verteporfin therapy on central visual field function

PURPOSE: To evaluate the effect of photodynamic therapy with verteporfin on the maintenance of central visual field function. DESIGN: Randomized controlled clinical trial. PARTICIPANTS: Forty-six consecutive patients with subfoveal choroidal neovascularization (CNV) caused by age-related macular degeneration including a classic component were randomly assigned. Thirty-three participants received standard verteporfin therapy, and 13 received placebo and laser treatment. METHODS: The trial was performed as a single-center, double-masked study. Patients were examined before therapy and continuously in 3-month intervals during 2 years of follow-up. A scanning laser ophthalmoscope (SLO) was used to perform macular microperimetry. Absolute and relative scotomas were documented at each visit, and size was measured in square millimeters. MAIN OUTCOME MEASURES: The change in size of central scotoma in the verteporfin group compared with the placebo group. RESULTS: An absolute scotoma was seen in 88%, and a relative scotoma was seen in 100% of eyes before therapy. Absolute defects were associated with the classic CNV component localized angiographically. In the verteporfin group, the absolute scotoma grew from 2.5 mm(2) at baseline to a final size of 7.3 mm(2) at month 24. In the placebo group, the mean lesion size of the absolute scotoma enlarged from an initial size of 2.7 mm(2) to 31.5 mm(2) after 24 months. The relative scotoma increased from 7.9 mm(2) at baseline to 20.8 mm(2) at month 24 in the verteporfin group, whereas a progression from 8.5 mm(2) initially to 48.3 mm(2) at the final presentation was measured in the placebo group. Statistical analysis showed that both the mean absolute and relative scotoma sizes were significantly smaller in the verteporfin group than the placebo group for all intervals from 6 to 24 months (P<0.001). CONCLUSIONS: Documentation of macular function with SLO perimetry demonstrated a significant benefit of verteporfin therapy for the preservation of the central visual field. Absolute and relative scotoma sizes remained smaller after therapy. This may influence reading ability and visual rehabilitation.     

Metastatic breast carcinoma to the vitreous

PURPOSE: To evaluate the clinical and pathologic findings in two patients with prior breast carcinoma who underwent diagnostic vitrectomy for vitreous opacities and preretinal membrane. METHODS: The clinical histories and ophthalmic findings in two patients were reviewed. Vitrectomy specimens from the patients were processed by cytospin and standard tissue techniques, stained with hematoxylin and eosin, and examined immunohistochemically for cytokeratins. The original breast carcinoma specimens were reviewed. RESULTS: The vitreous in both patients contained malignant cells with cytologic features consistent with metastatic carcinoma. Immunohistochemical stains were positive for cytokeratins in the cells. The cytologic findings in the vitreous cells resembled the primary breast carcinoma. CONCLUSIONS: Breast carcinoma may metastasize to the vitreous, most likely via the retina. The clinical manifestations include vitreous cell and preretinal membrane.     

Laparoscopic staging compared with imaging techniques in the staging of advanced cervical cancer

OBJECTIVE: We evaluated the evidence of laparoscopy for decision regarding treatment options in advanced cervical cancer patients. METHODS: One hundred nine consecutive patients with cervical cancer FIGO stage Ib2 and higher underwent laparoscopic staging of the extent of disease. Laparoscopic and histopathologic evaluation of tumor involvement of the paraaortic and pelvic lymph nodes, wall of the bladder, and rectal pillar was compared with preoperative findings of MRI and/or CT. RESULTS: Paraaortic lymphadenectomy was performed in 101 (92.7%) patients and 21 (19.3%) patients had positive paraaortic lymph nodes. Pelvic lymphadenectomy was performed in 75 (68.8%) patients and 20 (26.7%) patients had positive pelvic lymph nodes. In 11 patients (11.5%) infiltration of the bladder and in 6 patients (6.25%) infiltration of the rectal pillar or cul-de-sac was found. Intraoperative complications associated with laparoscopic staging occurred in 3.7% of patients. The negative predictive value for the evaluation of paraaortic or pelvic lymph nodes, the bladder wall, rectal pillar, and cul-de-sac ranged from 73% (CT for pelvic lymph nodes) to 96% (MRI for bladder wall). Lack of information about the extent of disease was adjusted on the basis of laparoscopic findings in 24 (22%) patients and improved treatment plans. CONCLUSION: Laparoscopic staging of patients with advanced cervical cancer is accurate, associated with low morbidity, and helps to adjust treatment according to extent of disease.     

Changes in confocal indocyanine green angiography through two years after photodynamic therapy with verteporfin

PURPOSE: To evaluate vascular changes documented by confocal indocyanine green angiography (ICGA) through 2 years after photodynamic therapy (PDT) with verteporfin of neovascular age-related macular degeneration (AMD). DESIGN: Single-center, 2-year, randomized, double-masked, interventional, placebo-controlled trial (subset from Treatment of AMD with PDT Study [TAP]). PARTICIPANTS: Sixty patients with subfoveal choroidal neovascularization (CNV) resulting from AMD. INTERVENTION: Patients were randomized in a ratio of 2:1 to a standard regimen using verteporfin therapy at a drug dose of 6 mg/m(2) body surface area and a light dose of 50 J/cm(2) or a sham treatment with placebo infusion and light exposure. Retreatments, if persistent fluorescein leakage from CNV was documented, were scheduled at 3-month intervals for up to 2 years. Confocal ICGA with tomographic sections was performed at baseline and continuously at the month 3, 6, 12, and 24 examinations using a standardized protocol. MAIN OUTCOME MEASURES: Analysis included the size of the neovascular net, the area of late hyperfluorescence, and choroidal hypofluorescence during early- and late-phase imaging. RESULTS: In the verteporfin-treated group, the mean size of the CNV and the mean area of late leakage consistent with active leakage or staining showed no further enlargement at month 12 and were reduced at month 24. In the placebo-treated group, new vessels grew threefold compared with baseline and exhibited persistent late hyperfluorescence resulting from leakage at 24 months. Associated choroidal hypofluorescence within the treated area was significantly increased in eyes treated with verteporfin PDT compared with the control group during the first year, persisted during all ICGA phases, and was irreversible during follow-up. Image analysis revealed choroidal hypoperfusion with choriocapillary dropout, which correlated with chorioretinal atrophy clinically. Progressive destruction of choroidal integrity by fibrosis in control eyes led to a similar extent of collateral hypofluorescence in both groups through the 24-month examination. CONCLUSIONS: Indocyanine green angiography is an important adjunct in the identification of vascular effects associated with verteporfin PDT. Repeated treatments effectively arrested CNV growth and reduced leakage activity. The collateral impairment of choroidal perfusion appears to influence the visual outcome of the treatment.     

Photodynamic therapy: extended indication

OBJECTIVE: Evaluation of efficacy of photodynamic therapy (PDT) for classic choroidal neovascularization (CNV) beyond the common indication. METHODS: A group of 256 patients was treated with photodynamic therapy from January to December 2000. Ten of these patients had a predominantly classic CNV due to angioid streaks (5), parafoveal telangiectasia (2), or chorioretinitis (3). In two patients an idiopathic origin of the CNV was presumed. Another 21 patients showed a juxtafoveal classic membrane (12) or a recurrence after laser photocoagulation (9). Visual acuity was evaluated, also in correlation to age and CNV size. Continuous follow-up of CNV and leakage size was performed with fluorescein angiography. RESULTS: Overall 85% of the patients showed visual stabilization or improvement during an average observation period of 10.5 months. A correlation was found between age and visual improvement favoring younger patients; however, no correlation was found between visual improvement and CNV size. CNV and leakage size decreased moderately over the 9-month follow-up from 1.81/3.45 mm(2) to 1.61/2.60 mm(2). CONCLUSION: PDT shows efficacy for classic choroidal neovascularization beyond the common indication.     

Invertebrate models of neurologic disease: Insights into pathogenesis and therapy

The search for cures of human diseases can be very slow, expensive, and serendipitous. Roughly five decades of basic research in a handful of model systems has revealed that most animals are quite similar to one another especially at the cellular and molecular levels. The commonalities allow one to use animal models to investigate human disease mechanisms. Here, we review contributions demonstrating the use of invertebrate models to investigate human neurodegenerative diseases. We conclude that the integration of fly and worm models into programs seeking to identify therapeutic strategies for neurodegenerative disease can significantly speed progress toward finding cures for these devastating diseases.     

Establishing a new technique of laparoscopic pelvic and para-aortic lymphadenectomy

OBJECTIVE: To assess the number of operations necessary to develop and standardize a laparoscopic approach to pelvic and para-aortic lymphadenectomy, with radicality and number of complications as quality markers. METHODS: Over 4 years, 108 women had complete laparoscopic pelvic and para-aortic lymphadenectomies combined with laparoscopy-assisted radical vaginal hysterectomies for primary therapy of cervical cancer. Complete data and videotapes were available for 99 women. Operating time and radicality for specific anatomic subareas were measured by review of video documentation and histologic lymph node counts. Intra- and postoperative complications were recorded prospectively. To analyze the progress of surgery, we compared two groups of women, one operated on at the beginning of our study (early group, subjects 6-35) and one operated on in the final period of the study (late group, subjects 79-108). RESULTS: The operating time for pelvic and para-aortic lymphadenectomy increased constantly. Comparing the early and late groups for para-aortic lymphadenectomy, there was an increase in mean operating time (34.8 versus 73.2 minutes; P < .001) and mean histologic lymph node yield (5.1 versus 10.6; P < .001). For pelvic lymphadenectomy, mean operating time increased slightly (60.7 versus 69.7 minutes; not significant) but mean histologic lymph node count decreased over time (24.3 versus 21.0; not significant). Retrospective evaluation of videotapes showed that the radicality of lymphadenectomy improved continuously in all evaluated subareas. CONCLUSION: Establishment of a protocol for para-aortic and pelvic lymphadenectomy took 100 operations. Video documentation was a more reliable indicator of progress in technical performance than were histologic lymph node counts.     

No relationship between cerebral blood flow velocity and cerebrovascular reserve capacity and contemporaneously measured glucose and insulin concentrations in diabetes mellitus

Blood glucose and insulin concentrations have been reported to influence cerebral hemodynamics. We studied the relationship between actual blood glucose and insulin concentrations and resting cerebral blood flow velocity in the middle cerebral artery and cerebrovascular reserve capacity after acetazolamide stimulation. Thirty-six insulin-dependent diabetic patients in a state of good glycemic control were studied. Blood samples were taken for determination of glucose and insulin concentrations. Subsequently we measured resting cerebral blood flow velocities in supine position using transcranial Doppler, administered 1 g acetazolamide intravenously, and repeated the measurements after 5, 10, 15 and 20 minutes. Cerebrovascular reserve was calculated as the maximal percent increase after acetazolamide stimulation. Multiple regression was used for statistical analysis. Blood glucose levels were not correlated with resting blood flow velocity (R = 0.21, p = 0.22) nor cerebrovascular reserve capacity (R = 0.17, p = 0.32). Similarly, no correlation was found between insulin concentrations, resting cerebral blood flow velocity (R = 0.24, p = 0.22) and cerebrovascular reserve (R = 0.26, p = 0.24). Studying patients with long-term (> 10 years) and short-term (≤ 10 years) disease duration yielded the same lack of correlation. We conclude that there is no significant correlation between contemporaneously measured glucose and insulin concentrations and either cerebral blood flow velocity or cerebrovascular reserve capacity in the middle cerebral artery in type 1 diabetic patients with good control. Received: 13 November 1998 / Accepted in revised form: 17 December 1999     

Isolation of DICE1: a gene frequently affected by LOH and downregulated in lung carcinomas.

In the development and progression of sporadic tumors multiple tumor suppressor genes are inactivated that may be distinct from predisposing cancer genes. Previously, a tumor suppressor locus on human chromosome 13q14 that is distinct from the retinoblastoma predisposing gene 1 (RB1) has been identified in lung, head and neck, breast, ovarian and prostate tumors. By an approach that combines genomic difference cloning and positional cloning we isolated the cDNA of a novel gene (DICE1) located at 13q14.12-14.2. The DICE1 gene is highly conserved in evolution and its mRNA is expressed in a wide variety of fetal and adult tissues. The DICE1 cDNA encodes a predicted protein of 887 amino acids corresponding to an 100 kD protein that shows 92.9% identity to the carboxy-terminal half of the mouse EGF repeat transmembrane protein DBI-1. The DBI-1 protein interferes with the mitogenic response to insulin-like growth factor 1 (IGF-I) and is presumably involved in anchorage-dependent growth. When compared to normal lung tissue expression of the DICE1 mRNA was reduced or undetectable in the majority of non-small cell lung carcinomas analysed. The location of the DICE1 gene in the region of allelic loss, its high evolutionary conservation and the downregulation of expression in carcinoma cells suggests that DICE1 is a candidate tumor suppressor gene in non-small cell lung carcinomas and possibly in other sporadic carcinomas.