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Biomedical subjects

P Wolf

Publications and source records attributed to P Wolf.

At least 91 records · Page 5Linked to original sources

Effects of nifedipine on rhythmic synchronous activity of human neocortical slices.

The antiepileptic effect of the dihydropyridine calcium channel blocker nifedipine was tested in neocortical slice preparations (n=27) from patients ranging in age from four to 46 years (mean=25) who underwent surgery for the treatment of intractable epilepsy. Epileptiform events consisted of spontaneously occurring rhythmic sharp waves as well as of untriggered epileptiform field potentials induced by omission of Mg(2+) from the superfusate, or epileptiform field potentials elicited by application of bicuculline and triggered by single electrical stimuli. (1) Spontaneous rhythmic sharp waves (n=6): with nifedipine (40micromol/l), the repetition rate was decreased down to 30% of initial value, whereas the area under the field potential remained nearly unchanged. (2) Untriggered low Mg(2+) epileptiform field potentials (n=6): with nifedipine (40micromol/l) the area under the field potentials was reduced while the action on the repetition rate was ambiguous. (3) Triggered bicuculline epileptiform field potentials (n=15): with nifedipine (40micromol/l; n=4), no antiepileptic effect was found. There was, however, a marked increase in the area under the epileptiform field potentials. The area under the field potentials was reduced only at a dosage of 60micromol/l (n=11). This effect was stronger when nifedipine was applied with a K(+) concentration raised from 4 to 8mmol/l. The results show that the calcium channel blocker nifedipine is able to reduce differential epileptiform discharges in human neocortical tissue. These observations are in line with previous findings, suggesting that calcium flux into neurons is involved in epileptogenesis. The present results therefore support the idea that some organic calcium antagonists may be useful in human epilepsy therapy, although the etiology of epileptic seizures seems to be a critical factor for the efficacy of the drug.

Adolescent↗

Transcatheter cryoablation of ventricular myocardium in dogs.

INTRODUCTION: Surgical cryoablation, a highly effective technique used during antiarrhythmic surgery, produces voluminous, histologically uniform and discreet myocardial lesions. In contrast, radiofrequency (RF) catheter ablation, which as a result of its less invasive nature has largely supplanted antiarrhythmic surgery, produces smaller, histologically heterogeneous myocardial lesions. Since small lesion size and heterogeneity may reduce antiarrhythmic efficacy, we sought to reproduce the large, histologically homogeneous lesions created by surgical cryoablation, using a catheter cryoablation system (Cryogen, Inc., San Diego, CA) in the canine ventricle. METHODS AND RESULTS: In seven dogs, nineteen ventricular lesions (two right and seventeen left) were created with a 10F cryoablation catheter with either a 2 or 6 mm tip. In one dog AV node ablation was also performed. For each 'freeze', catheter tip nadir temperature, lesion width, depth, and transmurality were recorded, and lesion volume calculated. Average tip nadir temperature was -79.6+/-4.9 degrees C. Cooler nadir tip temperature was associated with deeper (p=.007) and more voluminous lesions (p=.042), and a greater likelihood of lesion transmurality (p=.034). Average lesion volume was 500+/-356 mm(3). No other variables predicted lesion volume or transmurality. Histologically, the catheter cryoablation lesions were sharply demarcated and homogeneous. The single freeze performed at the AV junction produced complete AV block. One complication, catheter rupture following its repetitive use, resulted in a coronary air embolus and death. CONCLUSION: Catheter cryoablation of canine ventricular myocardium produced voluminous, discrete, transmural lesions, which might be effective for ablation of ventricular tachycardia. Lesion volume and transmurality were dependent on catheter tip nadir temperature.

Analysis of Variance↗

Extended extracorporeal photochemotherapy with extracorporeal administration of 8-methoxypsoralen in systemic sclerosis. An Austrian single-center study.

BACKGROUND: Extracorporeal photochemotherapy (EXP) is an immunomodulating therapy that has been used in a limited number of patients with systemic sclerosis (SSC) with controversial results. The present study was performed to evaluate the efficacy and safety of extended EXP with extracorporeal application of liquid 8-methoxypsoralen (8-MOP) in the treatment of SSC. METHODS: Eleven women with progressive SSC of recent onset were treated for a period of 16-57 months. Skin changes, physical performance, extracutaneous manifestations, and quality of life were evaluated before initiation of EXP and at regular intervals thereafter. RESULTS: From the start to the last set of EXP, we observed an overall improvement and/or stabilization of skin changes and physical performance in 5 of 11 patients (45%). Extracutaneous manifestations deteriorated in 10 of 11 patients (91%) (P<0.05), and quality of life deteriorated in 9 of 11 patients (82%) from a mean score of 10 before, to 17 at the last set of EXP (P<0.05). No major side effects were noted. CONCLUSION: Extended EXP with extracorporeal administration of 8-MOP is a safe and well tolerated treatment modality. However, it provides only (minor) improvement of skin changes of a subset of SSC patients and does not beneficially influence extracutaneous manifestations and quality of life.

Adult↗

Topical treatment with liposomes containing T4 endonuclease V protects human skin in vivo from ultraviolet-induced upregulation of interleukin-10 and tumor necrosis factor-alpha.

Exposing human skin to ultraviolet radiation causes DNA damage, sunburn, immune alterations, and eventually, skin cancer. We wished to determine whether liposomes containing a DNA repair enzyme could prevent any of the acute effects of irradiation when applied after ultraviolet exposure. Fifteen human patients with a prior history of skin cancer were exposed to two minimal erythema doses of ultraviolet radiation on their buttock skin. Liposomes containing T4 endonuclease V or heat-inactivated enzyme were applied immediately and at 2, 4, and 5 h after ultraviolet irradiation. Transmission electron microscopy after anti-T4 endonuclease V-staining and immunogold labeling on biopsies taken at 6 h after ultraviolet exposure revealed that the enzyme was present within cells in the skin. Immunohistochemical DNA damage studies suggested a trend toward improved DNA repair at the active T4 endonuclease V liposome-treated test sites. Although the active T4 endonuclease V liposomes did not significantly affect the ultraviolet-induced erythema response and microscopic sunburn cell formation, they nearly completely prevented ultraviolet-induced upregulation of interleukin-10 and tumor necrosis factor-alpha RNA message and of interleukin-10 protein. These studies demonstrate that liposomes can be used for topical intracellular delivery of small proteins to human skin and suggest that liposomes containing DNA repair enzymes may provide a new avenue for photoprotection against some forms of ultraviolet-induced skin damage.

Administration, Topical↗

Epilepsy and catalepsy in Anglo-American literature between romanticism and realism: Tennyson, Poe, Eliot and Collins.

Epilepsy and catalepsy were not clearly separated in the minds of people in the early 19th century, and catalepsy may have been used as a diagnostic euphemism for epilepsy. Tennyson, in "The Princess" describes, under the diagnosis of catalepsy, probable temporal lobe epileptic dreamy states with derealization which serve as a metaphor of sexual and moral ambivalence, the poem's central theme. It seems that Tennyson knew such seizures from his own father who had been given a diagnosis of catalepsy. Poe gave his Berenice in the novella of the same title a diagnosis of epilepsy as a reason for a premature burial. However, there was a good deal of unlikelyhood in this, and when he came to this theme in "The Fall of the House of Usher" and in "The Premature Burial" he chose instead a diagnosis of catalepsy which fitted better with the plot. The fits of the title character in George Eliot's Silas Marner, diagnosed as catalepsy, would today rather be seen as epileptic twilight states. It would seem that this author drew from contemporary dictionary descriptions which described conditions similar to Marner's fits under the heading of catalepsy. In Eliot's "legend with a realistic treatment", the twilight states are a central factor in the plot and explain Marner's reclusion and passivity. In Poor Miss Finch by English realist Wilkie Collins, the post-traumatic seizures of Oscar, one of the main characters, their cause, their treatment with silver nitrate, and the subsequent discoloration of his skin are central supporting elements of a perfectly constructed plot. Collins gives an exact description of a right versive seizure with secondary generalisation, and how to deal with it. In none of these works seizures are seen in a negative light. They rather evoke reactions of sympathy and support.

Catalepsy↗

Does the timing of hypertonic saline resuscitation affect its potential to prevent lung damage?

Hypertonic saline (HS) resuscitation has been reported to prevent lung damage by suppressing neutrophil activation in animal models. Data on the effectiveness of HS to prevent organ damage in the clinical setting are inconsistent. We investigated whether the timing of HS administration relative to neutrophil activation could affect its potential to block neutrophil responses. Different likely clinical circumstances were simulated in vitro by exposing human neutrophils to HS at different time points before and after activation with N-formyl-methionyl-leucyl-phenylalanine (fMLP). The in vivo effect of using HS as a secondary resuscitation fluid was determined with a mouse model of hemorrhage. BALB/c mice were hemorrhaged (40 +/- 5 mmHg) for 1 h and partially resuscitated with HS or Lactated Ringer's (LR) 20 min before completing resuscitation with LR or HS, respectively. Neutrophil activation parameters were determined 2 h after complete resuscitation and lung damage was assessed after 24 h. The length of exposure to physiologically relevant HS levels (20 mM) determined the suppressive effect on in vitro neutrophil superoxide formation. HS treatment caused a transient state of suppression during which neutrophil activation was suppressed; however, HS was unable to suppress cells that were stimulated with fMLP before HS was added. Accordingly, in vivo lung damage was greater in animals that received HS after they had been partially resuscitated with LR compared to mice that received HS before LR (P < 0.05). We conclude that timing of exposure to HS affects neutrophil responses in vitro and may reduce the potential of HS resuscitation to prevent lung injury in vivo.

Animals↗

Optical monitoring of neuronal activity during spontaneous sharp waves in chronically epileptic human neocortical tissue.

Functional changes in neuronal circuitry reflected in spontaneously occurring synchronous sharp field potentials (SSFP) have been reported to occur in human brain suffering from chronic epileptogenicity but not in primary nonepileptic tissue from peritumoral resectates. Voltage sensitive dyes and fast imaging were used to visualize spontaneously occurring rhythmic depolarizations correlated to SSFP in chronically epileptic human neocortical slices obtained during epilepsy surgery. Localized and spatially inhomogeneous neuronal depolarizations were found to underlie spontaneous SSFP, which remained unchanged and spatially restricted to foci <750 micrometer diam even under epileptogenic (low-Mg(2+)) conditions. In cases where ictaform paroxysmal activity occurred in low-Mg(2+) medium, neuronal depolarizations were wide-spread but still spatially inhomogeneous, and the events were preferentially initiated at distinct foci. The findings suggest that small neuronal networks are able to establish and maintain synchronous rhythmic and epileptiform activity.

Action Potentials↗

Epilepsy in contemporary fiction: fates of patients.

Fictional accounts of epilepsy are of interest because they may convey information on images and public views of epilepsy which are not contained in medical texts. Thus, medical and nonmedical traditions together form the cultural history of epilepsy. Of the numerous possible aspects of epilepsy in fiction, this paper looks especially at the writers' background of knowledge about epilepsy: epilepsy as a handicap and a reason for social rejection, with special reference to epilepsy under the Nazi rule; threats to patients' lives; the motive of the child with epilepsy as a divine child; and epilepsy as a fate, and a reason for distinction. Literary writers may help their readers understand that a person's suffering and fighting a condition like epilepsy very much deserves our attention and sympathy. Without being exclusive, the paper pays special attention to epilepsy in the writings of Canadian authors.

Adult↗

[Enzootic ulcer in the back of the tongue in cattle after ingestion of hay containing flower clusters of yellow bristle-grass].

Chronically recidivating enzootic ulcerations in the tongues of numerous milking cows in the Po river plain area in Italy. The animals were permanently kept indoors in cubicle houses and fed by hay containing high amounts of ripe yellow bristle grass (Setaria glauca (L.) Beauv. [= S. pumila Poiret]). The panicled parts of the culms were found to be the cause of the massive injuries.

Animal Feed↗

Use of von Willebrand diseased kidney as donor in a pig-to-primate model of xenotransplantation.

BACKGROUND: The coagulation process in hyperacute and delayed xenograft rejection is essential and depends upon platelet adhesion and aggregation. The initial binding of platelets to the damaged endothelium is due to the interaction of the platelet receptor glycoprotein Ib with von Willebrand factor (vWF), which is present on activated endothelial cells and bound to the subendothelial matrix. We hypothesized that the use of organs from animals with homozygous von Willebrand disease (vWD), severely deficient in vWF, might prevent the thrombosis encountered in delayed xenograft rejection. METHODS: Ten baboons were treated by extracorporeal immunoadsorption of xenoreactive natural antibodies (XNA) through the donor pig liver to inhibit hyperacute rejection and received heterotopic vWD or control pig kidney xenografts. XNA levels, coagulation, and platelet activation markers were studied, and specimens of rejected kidneys were analyzed histologically. RESULTS: Although XNA depletion was comparable in both groups, neither kidney function nor survival times of control (n=5) or vWD (n=5) porcine kidneys showed any difference. Platelet and coagulation activation was evidenced in both groups after surgery and at rejection time. Immunohistochemical analysis revealed a weak endothelial vWF immunostaining in the rejected vWD kidneys, whereas it was undetectable in the nongrafted vWD kidneys, suggesting the deposition of baboon plasma vWF on the porcine vessels. CONCLUSIONS: The use of vWD organs did not improve the survival time of grafted kidneys in this xenotransplantation model. Further studies on the use of vWD organs, in association with other therapeutic approaches, such as complement inhibition, are nevertheless necessary to evaluate the usefulness of vWF deficiency as an adjunctive therapy to decrease the coagulation process during xenograft rejection.

Animals↗

Narrowband (311-nm) UV-B therapy for small plaque parapsoriasis and early-stage mycosis fungoides.

BACKGROUND: Broadband UV-B phototherapy has been used for many years in the treatment of small plaque parapsoriasis (SPP) and early-stage mycosis fungoides (MF). Our purpose was to investigate the effect on these diseases of narrowband (311-nm) UV-B therapy, which was recently established for the treatment of psoriasis and found to be more effective than broadband UV-B therapy. OBSERVATIONS: Twenty patients (5 women, 15 men; age range, 39-85 years) with histologically confirmed SPP or early-stage MF were enrolled. Six patients had early-stage MF (patch stage), and 14 had SPP. Treatment with 311-nm UV-B was given 3 to 4 times a week for 5 to 10 weeks. In 19 patients, lesions completely cleared after a mean number of 20 treatments (range, 14-29 treatments) and a mean cumulative UV-B dose of 16.3J/cm2 (range, 7.4-36.4 J/cm2) within a mean time of 6 weeks (range, 5-10 weeks). Biopsy specimens taken immediately after the end of phototherapy showed only sparse inflammatory infiltrates but no signs of SPP or MF. Relapses at cutaneous sites occurred in all patients within a mean time of 6 months (range, 2-15 months). CONCLUSIONS: Narrowband UV-B therapy is an effective short-term treatment modality for clearing SPP and early-stage MF. However, the treatment response did not sustain long-term remission. Further studies are necessary to examine how the clinical response to and follow-up after narrowband UV-B therapy compares with that of established phototherapy modalities in these diseases.

Adult↗

Mouse-to-rat testicle transplantation.

This report details mouse-to-rat testicular transplantation with immediate revascularization. Donor preparation involved grafting a long segment of aorta and inferior vena cava (IVC) containing the testicular artery and vein. The graft aorta and IVC were anastomosed to the rat aorta and IVC, respectively. Vasovasostomy was completed and the scrotal epithelia were anastomosed to draw the graft toward the host scrotal sac. Twenty-nine of 53 transplants were determined to be viable. Histologically, 6- to 18-hr-old grafts displayed moderate to minimal polymorphonuclear neutrophil (PMN) infiltrates. Ischemia set in somewhere between 18-24 hr postoperatively. Beyond 24 hr the grafts displayed progressive infiltration of PMN and perivascular and intertubular lymphocytes, disorganization of the germinal epithelium, and cessation of spermatogenesis.

Animals↗

Long-term fate of heterotopic liver transplants in rats with portal vein inflow only.

Previous studies have suggested that hepatic arterial flow in heterotopic partial liver transplants is necessary to ensure graft survival and regenerative capacity. This report presents findings in a syngeneic rat strain (Lewis) that partial liver transplants can be successfully heterotopically transplanted in the long term with the only inflow coming from the portal vein. When the host liver undergoes a nearly complete resection at 3-4 weeks, the transplanted liver regenerates to maintain the health of the host. Moderate to massive hepatocellular necrosis occurs in the first 3 months postoperatively, with recovery by 4-5 months. Liver transplants 8-10 months postoperatively appear architecturally normal. No host liver tissues were found to be regenerating after subtotal host liver resection. We conclude that portal vein reconstruction without hepatic arterial inflow can sustain a partial liver transplant in the long term, replacing the function of the host liver.

Anastomosis, Surgical↗