Efficacy of a patient-training videotape on motor fluctuations for on-off diaries in parkinson's disease

Patient on-off diaries are used in clinical trials, but a method to assure agreement between patient and examiner has never been developed. We tested whether a patient-teaching tape increased the rate of agreement between patient diary ratings and simultaneous neurologic assessment by a trained professional. A total of 32 consecutive patients who had Parkinson's disease with motor fluctuations independently completed a 4-h on-off diary (nine ratings) at the same time as an examiner. Those with <80% agreement with the examiner (n = 20) were randomized to view either a training tape that showed motor fluctuations (experimental group) or another videotape of general patient educational material (control group). All patients then underwent the same 4-h assessment of motor fluctuations. To test for long-term retention, they returned 1 month later and, without reviewing the videotape, underwent a final 4-h correlation assessment. After the training tape, the experimental group showed significant improvement, whereas the control group showed no improvement. Furthermore, another month later, the improvement in the experimental group was retained. Based on these findings, we suggest that future clinical trials assessing motor fluctuations incorporate this tape into their basic methodology.     

Leukocyte and plasma N-laurylsphingosine deacylase (ceramidase) in Farber disease

Severe deficiency of acid ceramidase activity (4-5% of normal) was demonstrated in cultured skin fibroblasts, leukocytes and plasma from a 1-year-old boy who was diagnosed as being affected with Farber disease. Determination of ceramidase activity in plasma was achieved by a highly sensitive assay employing a ceramide substrate containing radiolabeled C12 N-acyl moiety (N-lauryl). The enzyme activity in the parents' leukocytes and plasma was found to be reduced to 18-47% of the respective normal values, and that determined in a plasma specimen from a patient with I-cell disease was about 4 times elevated above the normal level.     

A stereological study of the human ovarian surface epithelium.

The surface of the ovary has been found to be composed of two types of epithelial cells called A and B cells which are found in their own respective zones, the A and B zones. A quantitative study was undertaken to determine the mean cell volumes and cell ultrastructure. Ovarian biopsies were taken from six women and A and B zones, having been identified by scanning electron microscopy, were re-embedded for transmission electron microscopy. Stereological measurements using point sampled intercepts were made on vertical sections and showed that B cells are significantly larger than A cells. The volume weighted mean cell volumes of the A and B cells were 237.3 microns 3 and 676.8 microns 3 respectively. The volume fractions of the nucleus and mitochondria were similar in the two cell types. Although the vesicle content of each type was similar, a large variation between cases made the interpretation difficult. The stereological tools used in this study proved to be easy and efficient estimators of surface cell ultrastructure and give an important direction for ultrastructural research.     

Balloon dilatation versus surgical revision of infra-inguinal autogenous vein graft stenoses: long-term follow-up

Although infra-inguinal autogenous vein graft stenoses may be treated by balloon dilatation (PTA) or surgical revision, the optimal approach is undefined. Over the last 7 years 24 PTA procedures were performed on 37 vein graft stenoses in 19 grafts. Graft stenoses were diagnosed from 2 to 72 (mean = 17.3) months after implantation. PTA was successfully completed in 23 (96%) of the 24 procedures including 18 (95%) of the primary, and 5 (100%) of the secondary procedures. Recurrent vein graft stenosis or graft thrombosis developed in 12 (67%) grafts from 3 to 47 (mean = 12.5) months after primary PTA. Long-term patency after primary PTA was 69% at 6, 29% at 12, and 22% at 36 months; secondary patency was 81% at 6, 45% at 12, and 27% at 36 months. During the same period vein graft stenosis in 7 fem-pop and 2 fem-tib grafts were surgically revised with an initial success rate of 100%, and 2 (22%) complications. Four (44%) of these grafts occluded from 1-17 (mean 6.2) months after repair, yielding a primary 5-year patency of 62%. Although vein graft stenosis may be safely, effectively, and repeatedly treated with PTA, long-term durability appears to be superior after surgical revision.     

Progesterone and environmental tobacco smoke act synergistically to exacerbate the development of allergic asthma in a mouse model

BACKGROUND: Asthma affects males and females differently. Females have a higher incidence than males after the onset of puberty. This suggests a hormonal component to the development of the disease. Progesterone, a female hormone, has previously been shown to illicit a T-helper type 2 (TH2) immune response similar to that seen in allergic asthma. Previous studies performed by our laboratory have shown that exposure to environmental tobacco smoke (ETS) enhances the immune response to allergens. OBJECTIVE: To determine if the combination of exposure to ETS and progesterone would further exacerbate the immune response in a mouse model of allergic asthma. METHODS: Female mice were ovariectomized and then implanted with time-release progesterone pellets. Mice were housed in either filtered air (FA) or ETS chambers and half were exposed to aerosolized house dust mite allergen (HDMA). Bronchoalveolar lavage was performed for cell differentials; lung and spleen cells were harvested to compare IL-4 and IFN-gamma production by ELISPOT. RESULTS: Progesterone pellet implantation resulted in increased serum progesterone levels (28.3+/-8.43 vs. 13.5+/-7.22 ng/mL in placebo-treated mice, P<0.0001). Serum total IgE levels were significantly greater in progesterone vs. non-progesterone treated animals that were also exposed to HDMA. ETS exposure enhanced total IgE levels as well. Lung homogenate cells from HDMA/progesterone-treated animals stimulated with Concavalin A produced significantly more IL-4 compared with HDMA/placebo-treated animals (200+/-17.6 vs. 146+/-17.5 spots/well, P<0.01 in ETS exposed animals and 221+/-28.9 vs. 167+/-23.4 spots/well, P<0.01 in animals housed in FA). HDMA/ETS-treated animals had higher eosinophilia in lavage than all other groups. CONCLUSION: Increased serum progesterone levels exacerbate the allergic asthmatic phenotype in a mouse model. These effects are further exacerbated by the addition of environmental tobacco smoke. Progesterone provides a major contribution to the gender differences seen in the development and elicitation of the asthmatic response.     

A not-so-basic case of metabolic alkalosis: an analysis featuring Leendert Paul and emphasizing Occam’s razor

A patient had the onset of a severe degree of metabolic alkalosis associated with a very large daily loss of diarrheal fluid. Because the expected acid-base disorder in this setting is metabolic acidosis, factors that could result in the markedly increased concentration of bicarbonate (HCO₃⁻) in plasma (P ₃) were sought. In our approach, there is an emphasis on electroneutrality, mass balance, a quantitative analysis, and the application of basic concepts in physiology at the bedside. We suggest that there were 3 major factors that could explain why the P ₃ was so high. First, a severe degree of extracellular fluid volume contraction was probably the most important factor that raised her P ₃. Second, there may have been an unusual way to have an electroneutral addition of HCO₃⁻ and removal of chloride ions from her extracellular fluid compartment. Third, the diarrheal fluid could have contained little HCO₃⁻ because of a down-regulated intestinal secretion of HCO₃⁻. This analysis challenges the traditional pathophysiology of metabolic alkalosis.     

Inhibition of cis-diamminedichloroplatinum (II) — induced renal toxicity in the rat

Summary The hydroxyl-containing dithiocarbamates, sodium (di(hydroxyethl)-dithiocarbamate (NaY) and sodium N-methyl, N-dithiocarboxy-D-glucamine (NaG), appear to possess definite advantages over sodium diethyldithiocarbamate (DDTC) in reducing the cis-dichlorodiammineplatinum (Cis-Pt)-induced renal damage in rats given Cis-Pt as an IV bolus of 7.5 mg/kg 1 h before the IP administration of the dithiocarbamate. Renal damage, as estimated by blood urea nitrogen (BUN) values and serum creatinine levels, was less at all times up until sacrifice in animals given naY or NaG than in those given DDTC.An even more effective method for suppression of Cis-Pt renal toxicity is to use a combination of procedures. The most efficacious combination involves a 24-h pretreatment with DDTC or NaG plus acetazolamide and normal saline hydration 30 min before administration of Cis-Pt, followed by post-treatment with NaG. With this combination therapy renal function can be almost completely spared. Although DDTC or NaG pretreatment is highly effective when used in conjunction with NaG post-treatment, DDTC or NaG pretreatment alone has no renal sparing effect on renal function or renal platinum accumulation.In experiments in which antidotes were given 1 h after Cis-Pt and the animals were followed up for 75 days, a chronic interstitial nephritis at 75 days, suggesting a persistent cell-mediated immune response to Cis-Pt-induced renal damage, may be the basis for chronically abnormal renal function resulting from Cis-Pt. Treatment with all three dithiocarbamates, NaY, NaG, and DDTC, reduced the intensity of this cellular reaction and also reduced platinum levels in the kidneys.Although NaY and NaG are effective heavy metal chelators and renal function is spared and kidney platinum levels are substantially reduced by the dithiocarbamates, no parallel loss of antineoplastic activity by Cis-Pt on the rat Walker carcinoma was observed. Since the dithiocarbamates have no known human toxicity that would disqualify their clinical use, phase 1 clinical trials are indicated.This work was supported in part by the Natural Sciences Committee of the College of Arts and Sciences, Vanderbilt University     

Adenosine 5′-triphosphate,uridine 5′-triphosphate,bradykinin, and lysophosphatidic acid induce different patterns of calcium responses by human articular chondrocytes

Small calcium-mobilizing inflammatory mediators have been implicated in joint pathology. Here we demonstrate that bradykinin, adenosine 5′-triphosphate, uridine 5′-triphosphate, and lysophosphatidic acid raise the intracellular calcium concentration ([Ca²⁺]_i) in human articular chondrocytes. Heterologous cross-desensitization experiments showed that the uridine 5′-triphosphate response was abolished by prior treatment with adenosine 5′-triphosphate and conversely, that the adenosine 5′-triphosphate response was abolished by prior treatment with uridine 5′-triphosphate: this indicated competition for the same receptor site, whereas bradykinin and lysophosphatidic acid did not compete with other ligands. Pretreatment with thapsigargin abolished ligand-mediated Ca²⁺ responses but not vice versa: this confirmed that Ca²⁺ release occurred from intracellular stores. Single-cell analysis of Fura-2 acetoxymethyl ester loaded chondrocytes showed mediator-dependent patterns of oscillatory Ca²⁺ changes in a subset of cells when challenged with submaximal concentrations of bradykinin, adenosine 5′-triphosphate, or uridine 5′-triphosphate in the presence of extracellular Ca²⁺. However, no oscillatory responses were seen after a challenge with lysophosphatidic acid. Therefore, although a number of different Ca²⁺-mobilizing ligands activate chondrocytes, the differences that occur in the temporal patterning of Ca²⁺ responses may result in unique mediator-dependent changes in cellular activity.     

Supraceliac aortic occlusion: A safe approach to pararenal aortic aneurysms

Twenty-four patients who underwent surgery for pararenal aortic aneurysms between January 1992 and April 1997 are reviewed. Eighteen patients had primary atherosclerotic aneurysms, three patients had symptomatic infected aneurysms, two patients had an aneurysm proximal to a prior aortic repair, and one patient had a pseudoaneurysm of a proximal aortic graft anastomosis. Thirteen patients underwent elective operation, five had an urgent operation, and six patients underwent an emergency procedure. Five patients had the proximal aortic clamp placed between the renal arteries (Group I), three patients had it placed between the superior mesenteric and the renal arteries (Group II), and 16 patients had it placed in a supraceliac location (Group III). Aneurysm size, age, sex, preoperative blood chemistries (including hemoglobin, hematocrit, liver function studies, and coagulation studies) were similar in all groups. Two patients in Group III were on hemodialysis preoperatively. Preoperative renal function (blood urea nitrogen and creatinine) was the same in all groups. Visceral ischémic time was 43.4 ± 9.37 min to the distal kidney in Group I, 26.6 ± 7.63 min in Group II, and 24.5 ± 6.22 min in Group III. Mean transfusion requirements were similar in all groups. Two patients in Group I required postoperative hemodialysis. No patient in either Group II or III developed renal insufficiency. Mortality was the same in each group but was related to the urgency of operation (elective 7.6%, urgent 40%, emergent 50%). Intrarenal clamping (Group I) was associated with more renal and gastrointestinal complications than either suprarenal or supraceliac clamping. Although suprarenal and supraceliac clamping had similar results, our preference is supraceliac clamping because it is technically easy to achieve and is associated with few end-organ complications.     

State licensure: a hidden villain in the manpower shortage.

It is clear that our profession has a serious manpower shortage which will probably be with us for quite some time. The multi association Summit on Manpower and other groups have posed numerous theories on how this problem occurred, and have compiled lists of reasons for the shortage. However, one item missing from every list is the state licensure of radiologic technologists. This article focuses on that point and is presented in an effort to make people realize that licensure has a significant impact on the problem and must be addressed as "a piece of the puzzle."