Use of photodynamic therapy in the palliation of massive advanced rectal cancer

Photodynamic therapy (PDT) is a relatively new form of cancer therapy utilizing a photosensitizer such as hematoporphyrin derivative. We conducted a pilot study to determine the efficacy of its use in palliating advanced rectal cancer, to determine toxicity, and to establish objective outcome criteria. Six patients with very advanced, usually recurrent rectal cancer were treated with PDT after being photosensitized with Photofrin II^®. A protocol was established to measure clinical and radiologic response to therapy. A new intraluminal delivery system was incorporated. Five patients had both clinical and radiologic responses to therapy. In two patients we observed such significant responses that they cannot be accounted for on a photobiologic basis alone. One patient developed a significant sunburn after discharge. There was no major toxicity of bleeding or sepsis even at maximum doses (200 J/cm²). We are confident that PDT has a role to play in rectal cancer and speculate as to future applications.     

The epidemiology of Parkinson's disease. A case-control study of young-onset and old-onset patients

While the cause of Parkinson's disease (PD) remains unknown, recent evidence suggests that certain external factors, ie, environmental agents, may act as neurotoxins, initiating the chain of oxidative reactions that ultimately destroy neurons in the substantia nigra. Young-onset PD might result from greater exposure to a putative neurotoxin. This hypothesis has rekindled interest in the epidemiology of PD. We therefore conducted a detailed analysis of various environmental exposures and early life experiences in 80 patients with old-onset PD (at an age older than 60 years), 69 young-onset patients (younger than 40 years), and 149 age- and sex-matched control subjects. Contrary to previous reports, we were unable to implicate well water or exposure to herbicides, pesticides, or industrial toxins as significant PD risk factors. A residential history of rural living was reported by more patient cases than control subjects and was marginally significant. On the other hand, at least one episode of head trauma "severe enough to cause vertigo, dizziness, blurred or double vision, seizures or convulsions, transient memory loss, personality changes, or paralysis" occurred significantly more often prior to disease onset in patients with both young-onset and old-onset PD than in control subjects (odds ratio = 2.7). When adjusted for head trauma and rural living, smoking was inversely associated with PD, as has been previously reported (odds ratio = 0.5). There were no significant differences in early life experiences or environmental exposures between young-onset and old-onset patients. We suggest that the risk of developing PD is influenced by a variety of factors.(ABSTRACT TRUNCATED AT 250 WORDS)     

Phenylacetic acid in human body fluids: high correlation between plasma and cerebrospinal fluid concentration values.

In a group of six Parkinsonian patients and 13 "controls" with non-Parkinsonian neurological disease, there was a high correlation between both free and conjugated phenylacetic acid concentrations in plasma and cerebrospinal fluid taken at about the same time. This compound is the major metabolite of phenylethylamine, the production of which may be disturbed in a number of neuropsychiatric illnesses. Thus plasma measurements might be employed clinically to provide an estimate of central changes in phenylethylamine economy. A small but significantly higher proportion of conjugated phenylacetic acid was present in the plasma (but not cerebrospinal fluid) of Parkinsonians compared with controls.     

Radionuclide scanning in pseudo-Kaposi's sarcoma.

Sodium pertechnetate Tc 99m radionuclide scanning is considered to be a sensitive indicator in detecting lesions of Kaposi's sarcoma, including occult infiltrations. This report describes a "false-positive" scan in a patient with acroanglodermatitis (pseudo-Kaposi's sarcoma); therefore, this technique may not be useful in the differential diagnosis of these two clinically and histologically similar diseases. We suggest, instead that the technetium scan may be helpful in deciding on the course of therapy in acroangiodermatitis by demonstrating the nature of the underlying vascular anomalies.     

Responses of fetal rat bone cells and bone organ cultures to the ionophore,A23187

The ionophore A23187 produced a rapid transient increase in the rate of calcium uptake by isolated fetal rat bone cells. There was no effect on calcium efflux or total cellular calcium. The magnitude of the effect on influx was amplified when the cell were incubated at 4°C. Cellular metabolic functions and resorption of cultured fetal rat bones (release of⁴⁵Ca from pre-labeled long bone) were affected by A23187 in a biphasic manner: cell cyclic AMP (cAMP) was increased by 0.1 and 0.3 g/ml of the ionophore, whereas 10 g/ml was either ineffective or lowered the cAMP levels. The high A23187 concentration abolished the stimulatory effects of parathyroid hormone and methylisobutylxanthine. Concentrations of 0.1 and 0.3 g/ml A23187 stimulated bone resorption. The effect was abolished by calcitonin. Ionophore concentrations above 1 g/ml produced less bone resorption. These higher concentrations antagonized the bone-resorbing effect of parathyroid hormone and 1,25-dihydroxyvitamin D₃. A23187 at 5 and 10 g/ml decreased bone cell lactate and ATP. Thus at low concentrations, A23187 produced effects on bone similar to those of parathyroid hormone, suggesting that calcium is the primary initiator of PTH-induced bone resorption. At the higher concentrations A23187 may have a general inhibitory effect on cell metabolism.     

A functional neuroanatomy of tics in Tourette syndrome

BACKGROUND: Tics are involuntary, brief, stereotyped motor and vocal behaviors often associated with irresistible urges. They are a defining symptom of the classic neuropsychiatric disorder, Tourette syndrome (TS), and constitute an example of disordered human volition. The neural correlates of tics are not well understood and have not been imaged selectively. METHODS: Event-related [(15)O]H(2)O positron emission tomography techniques combined with time-synchronized audio and videotaping were used to determine the duration of, frequency of, and radiotracer input during tics in each of 72 scans from 6 patients with TS. This permitted a voxel-by-voxel correlational analysis within Statistical Parametric Mapping of patterns of neural activity associated with the tics. RESULTS: Brain regions in which activity was significantly correlated with tic occurrence in the group included medial and lateral premotor cortices, anterior cingulate cortex, dorsolateral-rostral prefrontal cortex, inferior parietal cortex, putamen, and caudate, as well as primary motor cortex, the Broca's area, superior temporal gyrus, insula, and claustrum. In an individual patient with prominent coprolalia, such vocal tics were associated with activity in prerolandic and postrolandic language regions, insula, caudate, thalamus, and cerebellum, while activity in sensorimotor cortex was noted with motor tics. CONCLUSIONS: Aberrant activity in the interrelated sensorimotor, language, executive, and paralimbic circuits identified in this study may account for the initiation and execution of diverse motor and vocal behaviors that characterize tics in TS, as well as for the urges that often accompany them. Arch Gen Psychiatry. 2000;57:741-748     

Myositis specific autoantibodies as a new diagnostic criterion for idiopathic inflammatory myopathies

Myositis specific autoantibodies (MSA) are the most specific diagnostic criteria for idiopathic inflammatory myopathies (IIM). There is no evidence of MSA presence in patients with other neuromuscular or connective tissue diseases. MSA are associated with homogeneous clinical syndromes: antisynthetases with antisynthetase syndrome, anti-SRP with severe, resistant to treatment myositis, anti-Mi-2 with classic, benign dermatomyositis. Therefore it is important to include the myositis specific antibodies into routine diagnostic scheme of IIM.     

Results following surgery for recurrent Dupuytren's disease

This study was designed to assess the subjective and objective results following surgery for recurrent Dupuytren's disease. Nineteen patients (28 fingers) were treated surgically for recurrent contracture and were located for follow-up analysis at a median of 4 years (range, 1-15 years). Seventeen of 28 recurrences involved the small finger and 16 patients had at least one component of Dupuytren's diathesis. For the purpose of analysis the patients were divided into 3 groups: group A (total active range of motion [TAM] < 150 degrees ) consisted of 7 digits treated with limited fasciectomy and interphalangeal arthrodesis, group B (TAM >/= 150 degrees ) consisted of 8 digits treated with dermatofasciectomy and full-thickness skin graft, and group C (TAM >/= 150 degrees ) consisted of 13 digits treated with fasciectomy and local flaps. Total active range of motion reflecting the preoperative, immediately postoperative, and final follow-up values revealed that group C (fasciectomy and local flap) was the only group to maintain a statistically significant TAM improvement from preoperative (205 degrees ) to final follow-up (230 degrees ) analysis. Dermatofasciectomy and full-thickness skin grafting did not prevent recurrent contracture (preoperative TAM = 175 degrees; final follow-up TAM = 150 degrees ). Thirteen patients had abnormal Semmes-Weinstein monofilament testing and 8 had abnormal 2-point discrimination. There were 3 anesthetic digits. Despite these findings, 18 of the 19 patients were unconditionally satisfied with their experience and would undergo the procedure again.     

Role of platelet-activating factor in functional alterations induced by xenoreactive antibodies in porcine endothelial cells

BACKGROUND: Platelet-activating factor (PAF) is a phospholipid mediator of inflammation which has been implicated in rejection. The interaction of anti-alpha-galactosyl natural antibodies (anti-alpha gal Abs) with endothelial cells is the initial step for the development of xenograft rejection. In our study, we stimulated porcine aortic endothelial cells (PAEC) with anti-alpha gal IgG to investigate the synthesis of PAF from PAEC and its biological consequences. METHODS AND RESULTS: PAF was extracted and chromatographically purified from cultured PAEC stimulated with baboon anti-alpha gal Abs. The Abs induced a dose-dependent synthesis of PAF peaking after 30 min of incubation, and decreasing thereafter. Concomitant cell shape change, motility, and cytoskeleton redistribution were observed. These events were prevented by addition of a panel of PAF-receptor antagonists. An SV40 T-large antigen-immortalized PAEC line was engineered to express PAF acetyl-hydrolase (PAF-AH) cDNA, the major PAF-inactivating enzyme. These transfected cells exposed to anti-alpha gal Abs showed reduced cell contraction and motility compared with empty vector-transfected cells. Moreover, in PAEC stimulated with anti-alpha gal Abs, the synthesis of PAF promoted the adhesion of a monocytic cell line as shown by the inhibitory effect of PAF-receptor antagonists and of PAF-AH expression. Finally, studies on cell monolayer demonstrated an enhanced permeability 48 hr after exposure to anti-alpha gal Abs, and this increase was prevented by PAF-inactivation and by PAF-receptor blockade. CONCLUSIONS: These results demonstrate that on stimulation with anti-alpha gal Abs, PAEC synthetize PAF which can contribute to several vascular events involved in xenograft rejection.     

Respiratory syncytial virus genotypes and disease severity among children in hospital

OBJECTIVES: To determine the spectrum of N and G genotypes of respiratory syncytial virus (RSV) causing respiratory tract infection and whether particular genotypes are associated with severity of infection. PATIENTS AND METHODS: Nasopharyngeal aspirates (NPAs) were obtained from 114 infants with acute respiratory tract infection due to RSV over two seasons. Viral mRNA was extracted from NPAs or cultured virus, reverse transcribed, and the cDNA amplified by the polymerase chain reaction using primers directed to parts of the N and G gene respectively. Amplicons were separately digested with four different restriction endonucleases for each gene. The fragments were separated by agarose gel, electrophoresis, and the electrophoretic patterns used to assign the various genotypes. Disease severity was assessed as very mild (upper respiratory tract signs only), mild (coryza and signs of lower respiratory tract infection), moderate (requiring nasogastric or intravenous fluids), and severe (requiring oxygen or ventilation). RESULTS: Five of the six known N genotypes were detected, but NP4 and NP2 were found most frequently. There was no association between N genotype and disease severity. Six G (SHL) genotypes were detected. Significantly (p = 0.04) more of the infants infected with the SHL2 genotype had severe or moderate disease. CONCLUSIONS: During the seasonal peaks of RSV respiratory tract infection at least 10 different RSV genotypes cocirculated. While there is no association between N genotypes and disease severity, infection with the SHL2 G genotype appears to result in moderate to severe disease.