Trancranial Doppler Monitoring of Response to Therapy for Meningovascular Syphilis

Meningovascular syphilis is now quite uncommon, but there have been increasing reports in patients immunocompromised with human immunodeficiency virus. The response of syphilis affecting the central nervous system to antibiotic therapy remains a challenge. This is an even greater challenge in patients who have underlying compromise of the immune system. The authors present a 46-year-old male with recurrent stroke who was found to have cerebrospinal fluid compatible with syphilitic involvement of the central nervous system and a cerebral arteriogram, which revealed focal narrowing of the right middle cerebral artery. The baseline transcranial Doppler study demonstrated increased mean and peak flow velocity within the right middle cerebral artery. Despite a 10-day course of intravenous penicillin, with substantial improvement in the cerebrospinal fluid results, this flow velocity elevation persisted, in a remarkably consistent pattern, over a 4-month follow-up period. Thus, the involved vessel remained patent following treatment, but no clear resolution of the stenotic lesion was observed.     

Differential Contractile Response of Cultured Microvascular Pericytes to Vasoactive Agents

Objective: Microvascular pericytes may contract in two different ways: In the first, a circumferential or radial mechanical force applied at right angles to the long axis of the vessel may constrict the underlying vessel affecting blood flow and transmural pressure. Retraction and elongation of pericyte processes may also occur tangentially and at right angles to the vessel axis and alter microvessel permeability by changing the amount of ablumenal surface covered or the openness of interendothelial junctions. In this study, cultured pericytes were utilized as a model experimental system to determine if vasoactive stimulation changes their shape in a manner consistent with this hypothesis. Methods: Pericytes cultured from isolated rate capillaries were subjected to angiotensin II and histamine. Their response was monitored by measuring the area of nonyielding substrate covered by the pericytes and the manner in which their shape changed. Shape changes were quantified by calculating the surface area: perimeter perimeter ratios. Results: Histamine significantly reduced surface area covered and the surface area: perimeter ratio. The pericyte processes retracted, resulting in elongated, spindle-shaped cells. These effects were nullified by the H₁ blocker diphenhydramine suggesting a receptor-specific response. Angiotensin II also elicited contraction and reduced surface area, but the cells contracted laterally and longitudinally. The surface area: perimeter ratios also decreased. Conclusions: These results indicate that pericytes are capable of two types of contractile responses in culture, depending on the specific vasoactive stimulus.     

Permeability of 13 different gloves to 13 cytotoxic agents under controlled dynamic conditions.

PURPOSE: The permeability of 13 different gloves to 13 cytotoxic agents under controlled dynamic conditions is described. METHODS: Thirteen cytotoxic agents were prepared at the highest concentrations normally encountered by pharmacy personnel. Four glove types--neoprene, natural rubber latex, nitrile, and vinyl--were exposed to the cytotoxic agents for 15, 30, and 60 minutes. Tests were conducted using the middle finger of each glove. Linearity, reproducibility, and sensitivity were evaluated for each drug tested. Assays were run using liquid chromatographic tandem mass spectrometry (LC/MS/MS) and high-performance liquid chromatography with ultraviolet light (HPLC-UV). Permeability testing was conducted using an original system designed to evaluate dynamic constraints, such as rubbing, stretching, and tension. RESULTS: Linearity by LC/MS/MS and HPLC-UV was confirmed at concentrations up to 1000 ng/mL for all drugs. Most glove materials were permeable at rates below ASTM recommendations over the one-hour testing period. Vinyl was the most permeable material. Carmustine permeated the widest variety of materials. Due to the high sensitivity of the analytic methods, all materials displayed low but significant permeability for at least one drug after one hour. Higher resistance to permeation was recorded for all neoprene, some natural rubber latex, and one nitrile glove. CONCLUSION: Neoprene, natural rubber latex, and nitrile gloves displayed the highest resistance to permeation of the 13 cytotoxic agents studied. Additional factors, such as duration of exposure, glove thickness, and drug liposolubility and molecular weight, also affected permeability.     

Predictors of punding in Parkinson's disease: results from a questionnaire survey.

Dopamine replacement therapy (DRT) for Parkinson's disease (PD) has recently been linked to the development of a number of nonmotor behavioral control problems. Punding, one of these nonmotor problems, is a term used to describe complex, purposeless stereotyped behaviors such as the repetitive handling or sorting of objects. A self-report questionnaire was adapted to assess punding in the context of dysfunctional hobby-related activities. We report the results of a survey of PD outpatients from a PD research clinic (n = 141) and non-PD controls (n = 103); conducted to identify clinical and psychological factors predictive of punding behaviors. The PD group reported hobbies and activities, which scored significantly higher on the Punding Scale than controls. Higher impulsivity, poorer disease-related quality of life, younger age of disease onset, and concomitant daily medication dosage from dopamine receptor agonists were independently predictive of higher Punding Scale scores in the PD group. These findings are similar to those seen in dopamine dysregulation syndrome, and provide further evidence for the role of impulsivity and age at disease onset in DRT-related nonmotor behavioral problems in PD.     

High Recurrence Rates of Squamous Cell Carcinoma after Mohs'' Surgery in Patients with Chronic Lymphocytic Leukemia

BACKGROUND: Cutaneous cancers exhibit a much higher incidence in patients with chronic lymphocytic leukemia than in nonleukemic patients. Squamous and basal cell carcinomas also exhibit greater subclinical tumor extension in patients with chronic lymphocytic leukemia. OBJECTIVE: The purpose of this study was to estimate and compare the recurrence rates of squamous cell carcinoma after Mohs' surgery in patients with chronic lymphocytic leukemia compared with those in controls and to evaluate differences among squamous cell carcinoma size and histologic grade. METHODS: We retrospectively assessed the clinical histories, postoperative notes, and surgical photographs of patients with chronic lymphocytic leukemia and controls matched (2:1) for age, sex, and surgical year. Both patients and controls underwent Mohs' surgery for squamous cell carcinoma of the head and neck at the Mayo Clinic between March 1988 and April 1999. RESULTS: Twenty-eight patients who underwent Mohs' surgery for 57 squamous cell carcinomas had 7 recurrences. The cumulative incidence of recurrence on a per-tumor basis was 4.3% at 1 year, 14.8% at 3 years, and 19.0% at 5 years. Squamous cell carcinoma was seven times more likely to recur in patients with chronic lymphocytic leukemia than in controls (p = .003). The distribution of tumor histologic grade was not significantly different between patients and controls (p = .39). Maximum preoperative tumor diameters were clinically similar between patients and controls (median 15 mm vs 14 mm; p = .04). CONCLUSION: The recurrence rates of squamous cell carcinoma were significantly higher in patients with chronic lymphocytic leukemia. Squamous cell carcinomas in patients with chronic lymphocytic leukemia did not exhibit a significant difference in histologic grade or clinical difference in preoperative tumor size. Close surveillance for squamous cell carcinoma recurrence is warranted in patients with chronic lymphocytic leukemia.     

Endotoxin preconditioning protects against the cytotoxic effects of TNFalpha after stroke: a novel role for TNFalpha in LPS-ischemic tolerance.

Lipopolysaccharide (LPS) preconditioning provides neuroprotection against subsequent cerebral ischemic injury. Tumor necrosis factor-alpha (TNFalpha) is protective in LPS-induced preconditioning yet exacerbates neuronal injury in ischemia. Here, we define dual roles of TNFalpha in LPS-induced ischemic tolerance in a murine model of stroke and in primary neuronal cultures in vitro, and show that the cytotoxic effects of TNFalpha are attenuated by LPS preconditioning. We show that LPS preconditioning significantly increases circulating levels of TNFalpha before middle cerebral artery occlusion in mice and show that TNFalpha is required to establish subsequent neuroprotection against ischemia, as mice lacking TNFalpha are not protected from ischemic injury by LPS preconditioning. After stroke, LPS preconditioned mice have a significant reduction in the levels of TNFalpha (approximately threefold) and the proximal TNFalpha signaling molecules, neuronal TNF-receptor 1 (TNFR1), and TNFR-associated death domain (TRADD). Soluble TNFR1 (s-TNFR1) levels were significantly increased after stroke in LPS-preconditioned mice (approximately 2.5-fold), which may neutralize the effect of TNFalpha and reduce TNFalpha-mediated injury in ischemia. Importantly, LPS-preconditioned mice show marked resistance to brain injury caused by intracerebral administration of exogenous TNFalpha after stroke. We establish an in vitro model of LPS preconditioning in primary cortical neuronal cultures and show that LPS preconditioning causes significant protection against injurious TNFalpha in the setting of ischemia. Our studies suggest that TNFalpha is a twin-edged sword in the setting of stroke: TNFalpha upregulation is needed to establish LPS-induced tolerance before ischemia, whereas suppression of TNFalpha signaling during ischemia confers neuroprotection after LPS preconditioning.