Dexamethasone-induced effects on B-50/GAP-43 expression and neurite outgrowth in PC12 cells.

Undifferentiated PC12 cells contain detectable levels of the nervous-specific protein B-50/GAP-43. Upon treatment with NGF or change of culture medium, B-50/GAP-43 levels remained unchanged during the first 12 hours while neuritogenesis starts. Both, B-50/GAP-43 levels and neurite outgrowth peak at 24 hours. These results suggest that in PC12 cells the amount of B-50 already present is sufficient to support the start of NGF-induced neuritogenesis, presumably by translocation from cytosolic compartments to the membrane. Addition of DEX reversed the rise in B-50/GAP-43 levels induced by either the change of medium or by NGF. In contrast, neurite outgrowth was inhibited to a lesser extent, although after 36 hours of pretreatment with DEX neurite length was lower than control. NGF was capable of enhancing B-50/GAP-43 levels both in the presence and absence of DEX. This corroborates data from others, who concluded that DEX and NGF exert their effects through different mechanisms, e.g., transcription versus mRNA stabilization, respectively. The inhibitory effect of DEX under various conditions on both B-50 expression and neurite outgrowth in the normal PC12 cell line demonstrates the tight coupling of these parameters that might be indicative of a threshold effect of B-50 levels on neurite outgrowth.


Effects of chronic treatment of haloperidol and clozapine on levels of G-protein subunits in rat striatum.

Chronic administration of typical neuroleptic drugs, such as haloperidol, causes the supersensitivity of brain dopamine D2 receptor in striatum and limbic regions, while the atypical neuroleptic clozapine does not. In order to understand the mechanism of their action at a molecular level, studies were carried out to assess the effects of chronic treatment of these drugs on the levels of G-proteins in the rat striatum using the Western blot method. Results of the present study demonstrate that the treatment with haloperidol or clozapine, respectively, down-regulate or up-regulate the levels of G proteins. Quantitative immunoblotting, using site-directed specific antisera, demonstrated that chronic treatment with haloperidol down-regulates Gi alpha, Gs alpha, and beta subunits while chronic treatment with clozapine upregulates Gi alpha, Gs alpha, and beta subunits. Neither of these drugs has any effect on the levels of Go alpha.


Isolation and structural characterization of Drosophila TDVDHVFLRFamide and FMRFamide-containing neural peptides.

An extract of adult Drosophila melanogaster was separated by gel exclusion, ion exchange, and reversed-phase chromatography. Four peptides, each with an -ArgPheNH2 C-terminal sequence, were identified by radioimmunoassay. The primary sequences were determined by Edman degradation and confirmed by mass spectrometry and sequence-specific radioimmunoassay. Three of the peptides are encoded by Drosophila proFMRFamide: AspProLysGlnAspPheMetArgPheNH2 (DPKQDFMRFamide), ThrProAlaGluAspPheMetArgPheNH2 (TPAEDFMRFamide), and SerAspAsnPheMetArgPheNH2 (SDNFMRFamide). A novel Drosophila peptide ThrAspValAspHisValPheLeuArgPheNH2 (TDVDHVFLRFamide) was also isolated. TDVDHVFLRFamide is structurally related to peptides isolated from chicken, cockroach, locust, and snail; the cockroach, fruitfly, and locust peptides differ only by the N-terminal amino acid residue. Two Drosophila neural genes, dsk and FMRFamide, are known to encode -ArgPheNH2-containing peptides; however, neither encodes TDVDHVFLRFamide, indicating that Drosophila contains another precursor encoding -ArgPheNH2 peptides.


Crystallographic and chemical properties of Mg-containing apatites before and after suspension in solutions.

Mg-containing synthetic apatites were prepared and then incubated in unbuffered 0.9% NaCl solution and in buffered 0.1 M CH3COOK solution (pH 7.4) at 37 degrees C to examine the changes in their crystallographic and chemical properties after suspension in these solutions. After one month of incubation, the magnesium (Mg) content in the samples decreased greatly, especially in samples with higher Mg content. The a and c axis dimensions of the samples changed with the decrease of Mg content. On the other hand, Mg concentrations in both solutions increased more than the Ca concentrations. Mg-substituted beta-tricalcium phosphate (beta-TCP), or whitlockite, formed from solutions with high Mg concentration. These results show that Mg-containing apatites dissolve to a greater extent than Mg-free apatites with the subsequent reprecipitation of Mg-poor apatites. In addition, the high Mg/Ca in solution favoured the reprecipitation of Mg-containing beta-TCP.


Effect of magnesium deficiency on 15-hydroxyeicosatetraenoic acid in cultured human umbilical arterial endothelial cells.

Effects of magnesium deficiency on the production of 15-hydroxyeicosatetraenoic acid (15-HETE) and cytosolic free calcium concentration in human umbilical arterial endothelial cells were studied by radioimmunoassay. 15-HETE release by endothelial cells incubated with normal magnesium media (900 microM Mg2+) for 24 h was 2.2 +/- 0.3 ng/mg protein. 15-HETE release gradually increased in proportion to decrease of magnesium. Low magnesium media (180 microM Mg2+) caused an increase in 15-HETE release in a time-dependent manner. Cytosolic free calcium concentration of endothelial cells in normal magnesium media fluctuated between 129.4 nM and 134.2 nM during a 24 h period. Low magnesium media (180 microM Mg2+) caused a time-dependent rise in cytosolic free calcium concentration which is consistent with a time-dependent increase in H-HETE release. High magnesium medium (1800 microM Mg2+) did not have any effect on cytosolic free calcium concentration or 15-HETE production. In conclusion, 15-HETE release by endothelial cells was stimulated by increase in cytosolic free calcium concentration induced by magnesium deficient media. It is suggested that magnesium deficiency induces atherosclerosis via increase in 15-HETE production.


Influence of ethyl alcohol when given alone or in combination with potassium and/or magnesium supplements on ventricular fibrillation threshold levels in laboratory rats.

Five groups of rats were studied in an investigation to determine whether changes in the ventricular fibrillation threshold (VFT) occur when ethyl alcohol (EtOH) is given alone or in combination with K+ and/or Mg2+ supplements; the first group (n = 20) served as controls, the second (n = 18) was given only EtOH, the third (n = 18) EtOH+KCl, the fourth (n = 16) EtOH+MgCl2, and the fifth (n = 18) EtOH+MgCl2 + KCl for a 9 month period. Two rats from each group were killed on each day. One rat heart was perfused using the Langendorff apparatus and the other used for tissue electrolyte analyses. A significant fall in the mean VFT (9.7 +/- SD 1.9 mA vs 4.5 +/- 1.6 mA; P less than 0.0001) was noted in the rats given EtOH solution as drinking water for 9 months, and a significant increase in the VFT levels was seen in the Mg(2+)-supplemented group (9.7 +/- 1.9 mA vs 18.9 +/- 4.1 mA; P less than 0.0001) and in the K+ + Mg2+ supplemented group (9.7 +/- 1.9 mA vs 15.8 +/- 1.3 mA; P less than 0.0001) compared to controls. In addition, an increase in the heart rate was observed in the group supplemented with Mg2+ (213 +/- 8 beats/min vs 231 +/- 10 beats/min; P less than 0.0001) as well as in the group supplemented with K+ + Mg2+ (213 +/- 8 beats/min vs 222 +/- 10 beats/min; P less than 0.002) compared to controls. There was no significant change in the coronary blood flow (CF) in any group.(ABSTRACT TRUNCATED AT 250 WORDS)


Beneficial effects of a calcium antagonist, nifedipine, on death and cardiovascular calcinosis induced by dietary magnesium deficiency in adult mice.

The effects of nifedipine on the survival rate and the cardiovascular calcinosis were investigated in dietary magnesium (Mg)-deficient mice. Male mice aged 8 to 10 weeks were fed with a diet which was either normal (0.07%) or deficient (0.007%) in Mg for 30 d. Nifedipine was added to the Mg-deficient diet for 30 d in a concentration of 1000 ppm. About 65% of Mg-deficient mice died within 30 d. In contrast, all the nifedipine-treated mice survived for 30 d. Mg-deficient mice showed hypomagnesaemia and hypocalcaemia which were not influenced by nifedipine treatment. Aortic and cardiac calcium contents increased in Mg-deficient mice, and these increments were normalized by nifedipine treatment. These results suggest that the life-saving effect of nifedipine in Mg-deficient mice might relate, at least in part, to the prevention of a deleterious increase in Ca in cardiovascular tissues.


Serum and erythrocyte magnesium concentrations and migraine.

Most people suffering from migraine present a hypersensitivity of the cervico-facial muscles, which may be linked to magnesium deficit. This paper describes a comparative study of serum and erythrocyte magnesium levels in 79 migraine patients and 55 controls. Serum magnesium did not differ significantly in either group, but some values were quite low. On the other hand, there was a significantly greater erythrocyte magnesium deficit in persons suffering from migraine than in controls (in both female and male subjects). This fact correlates with the improved state of migraine patients (already ascertained in earlier studies) following treatment consisting of the intake of magnesium-rich water. The findings support the hypothesis of a magnesium deficit in people suffering from migraine and raise the problem of the relationship between migraine and other pathologies, including chronic magnesium deficit, latent tetany due to magnesium deficit, mitral valve prolapse, and allergy.


Magnesium and blood pressure. I. Animal studies.

The relationship between experimental magnesium deficiency and blood pressure is complex and still the subject of much debate. The effect of Mg deficiency and blood pressure in Wistar rats receiving a Mg deficient diet (0.080 g/kg) for 40 weeks was examined. Deficient rats, when compared to controls, showed an initial transitory phase of hypotension, followed by normalization of blood pressure and then hypertension beginning after 15 weeks on the deficient diet. During the whole experimental period, heart rate was significantly increased in deficient rats as compared to controls. The fact that hypotension resulting from Mg deficiency of short duration can be inhibited by antihistamines and by indomethacin suggests that various mediators seen during the inflammatory period of Mg deficiency could be involved. Mg deficiency of long duration was accompanied by hypertension. When Mg-deficient rats received the control diet for a period of 3 weeks, Mg supplementation only partially corrected the hypertension. The hypertension was not a consequence of stimulation of the renin-angiotensin system since the plasma renin activity was not modified and ACE activity was reduced. These deficient rats showed a significantly lower vasopressor response to noradrenaline than control rats. Several factors such as increase in collagen, changes in elastin and arterial elasticity, total lipid content, and calcifications may account for the hyporesponsiveness to contractile agonists.(ABSTRACT TRUNCATED AT 250 WORDS)


Magnesium and blood pressure. II. Clinical studies.

Magnesium deficit may be considered as a cardiovascular risk because of its aetiopathogenic role in the genesis of atherogenous dyslipidaemias and the so-called "idiopathic" mitral valve prolapse. It does not, however, constitute a major antihypertensive factor, though it may sometimes be an accessory co-factor. Plasma magnesium is generally normal in untreated hypertensive patients and normotension is the rule during magnesium deficit. An inverse relationship between magnesium and renin in the plasma of hypertensives has not been confirmed. In practice, plasma magnesium seems to be related to the evolution of the disease. An inverse correlation between blood pressure and erythrocyte total and free magnesium levels has been observed in diverse selected populations but no adjustment has been made in these studies for important covariables. A weak positive association between blood pressure and erythrocyte free magnesium was lost in a multivariate regression analysis. As a rule there is no difference between erythrocyte, leucocyte, and lymphocyte magnesium in hypertensives and controls. More often no relation between urinary magnesium and blood pressure is observed. Daily urine magnesium may be increased with increased excretion of urine adrenaline. Epidemiological data on dietary magnesium, particularly in drinking water, should be carefully scrutinized: these studies do not establish a major role for magnesium as an antihypertensive factor but confirm the importance of magnesium deficit as a nephrocardiovascular risk factor and sometimes gives support for a role of magnesium as an antihypertensive cofactor. The use of magnesium-depleting drugs in hypertensive patients may induce magnesium depletion which must be palliated.(ABSTRACT TRUNCATED AT 250 WORDS)


Inhibition of aluminium toxicity by magnesium and citric acid in tobacco tissue culture.

Using tobacco callus tissues the authors studied the antagonism of magnesium and aluminium, and the inhibition of aluminium toxicity by magnesium and citric acid, as expressed by their effect on growth and alkalod content. In response to an increase in the concentration of MgSO4 in the culture medium the fresh weight of the cultures significantly increased, while with an increase in Al2(SO4)3 growth decreased, 2 mM causing a high degree of inhibition. The toxic effect of aluminium was less marked when Mg was present at a concentration higher by an order (antagonistic inhibition). When citric acid was added to the culture medium, promoting complex formation with Al, the toxic effect of Al was not apparent. The nicotine content of the tissues was in each case inversely correlated with the magnitude of biomass formation.


Magnesium, adenosine triphosphate, and catecholamine complexes: application of new means of identifying solute-solute interactions of biological significance using NMR chemical shift data.

The interaction of magnesium ions with biomolecular species is fundamental to the regulation of many biological processes. A mathematical technique to investigate such interactions is described. The concept of a pseudo-formation curve is discussed and the relevance and applicability of such constructions to the study of solute-solute interactions is outlined. Analysis of curves based on the published variation of chemical shift data of various nuclei of adrenaline and dichloroisoprenaline in aqueous solution, in the presence of increasing concentration of the complex Mg-ATP, is described. Unambiguous indentification of specific interactions and the stability of the species produced is shown to be feasible. Some variation of the values of formation constants deriving from different nuclei reflects the significance of molecular environmental factors on the parameters used.


Cardiac emergencies in the cancer patient.

Cardiac emergencies may be encountered during the management of patients with cancer, both in those with underlying cardiovascular disease and those with no previous history of cardiac problems. Both surgical and medical cancer treatment modalities may exacerbate preexisting cardiac conditions. Some antineoplastic agents can adversely affect the coronary arteries, myocardium, or pericardium. It has also been recognized that cardiac damage due to radiotherapy and chemotherapy may become clinically significant many years after therapy has been completed. Treatment of urgent cardiac problems in the cancer patient may differ from that recommended for other patient groups, since many cancer patients are not ideal candidates for some of the newer cardiac agents. Management of these conditions must therefore be tailored to the individual patient.


Etiology and current management of cancer-related hypercalcemia.

Important new information has been gained concerning the etiology of cancer-related hypercalcemia and thus treatment recommendations are changing. The most common cause of hypercalcemia in cancer patients is the parathyroid hormone-like peptide, PTH-RP. Patients with elevated serum calcium due to elaboration of parathyroid hormone-like peptide commonly present with hypophosphatemia and a relatively resistant form of hypercalcemia. Our new knowledge has led to recommendations against massive amounts of IV fluids and large doses of diuretics, which restore normocalcemia in only a minority of patients. New potent drugs such as pamidronate and gallium nitrate directly inhibit accelerated bone resorption. Thus, consideration should be given to the early administration of antiresorptive drugs immediately after intravascular volume has been repleted and urinary output has been established.


Neuropsychotropic drugs as adjuncts in the treatment of cancer pain.

Opiates remain the mainstay of cancer pain treatment, used in a logical and stepwise fashion with adjunctive therapies as needed. Certain neuropsychotropic drugs may enhance the analgesia produced by opiates and may occasionally be used in place of opiates. Some of these drugs may also provide additional psychoactive benefits. The types of neuropsychotropic drugs that may be useful in treating cancer pain include the tricyclic antidepressants, anticonvulsants, neuroleptics, antihistamines, psychostimulants, and benzodiazepines, as well as systemic local anesthetics. This article reviews the general principles of using adjunctive medications to achieve maximal analgesic benefit with the least number of side effects, and describes each class of neuropsychotropic drug, their proposed mechanism of analgesia, and appropriate use in cancer patients.


Improving communication with cancer patients.

Although much more information is being disclosed to cancer patients than in the past, there is still considerable disagreement about how much information should be conveyed. This paper reviews the basic elements of informed consent, examines some of the major barriers to effective communication, and suggests ways in which physicians can enhance communication with their cancer patients. Physicians are urged to evaluate patients in terms of their coping and information-seeking styles and to keep in mind that most patients want information. In fact, studies show that giving patients adequate information usually impacts positively on their psychological and physical well-being.


Carotid endarterectomy in the elderly.

The records of 146 patients 80 years of age or older who underwent 183 carotid endarterectomy operations from 1964 through 1990 were reviewed to determine surgical risk. The indications for operation were asymptomatic patients with carotid stenosis (n = 36); ipsilateral transient ischemic attacks (n = 46); ipsilateral stroke (n = 28); ipsilateral retinal embolus (n = 15); nonlateralizing symptoms (n = 40); and asymptomatic side in patients with contralateral symptoms (n = 18). Postoperatively, three patients (1.6% of operations) had a stroke with a residual deficit and three (1.6%) died. All deaths were from myocardial infarction. For comparison, during the same time period, the combined stroke with residual deficit and death rate for patients less than 80 operated upon for similar indications was 3.5%. Since 80-year-old patients have a life expectancy of at least five years, the authors conclude that elderly patients should be evaluated for carotid endarterectomy using criteria similar to that used for younger patients.


Early results of infrainguinal arterial reconstruction with a modified biological conduit.

We implanted 112 glutaraldehyde-fixed bovine carotid artery grafts (BioPolyMeric [BPM]) for infrainguinal reconstruction in 107 legs of 98 patients. Indications for surgery were disabling claudication in 28%, rest pain in 33% and tissue loss in 39%. In 32%, BPM bypass followed failed ipsilateral reconstruction. Autologous vein was either absent or inadequate in 60% of cases. BPM was used preferentially over vein in above-knee bypasses. The distal anastomosis was to the above-knee popliteal artery in 40%, to the below-knee popliteal artery in 35%, and to the tibial arteries in 25%. Follow-up was available from one to 25 months, with a mean of nine months. Wound complications developed after 9% of operations, including seven (6%) graft infections. Both patent grafts that became infected were salvaged. Four patients (4%) died within 60 days of surgery due to cardiac complications. Life-table primary and secondary patencies of all grafts were 64% and 65% at one year, and 48% and 62% at two years, respectively. The only factor significantly affecting graft patency was the location of the distal anastomosis (p < .01). Primary patencies at one and two years to the above-knee popliteal artery were 90% and 80%, to the below-knee popliteal artery were 56% and 37%, and to the infrapopliteal arteries were 34% and 26%. Bypass to 16% of extremities resulted in amputation, including 5% that were amputated with patent grafts. No limb loss occurred as a result of operation for claudication. In conclusion, BPM grafts provide early results comparable to saphenous vein above the knee.(ABSTRACT TRUNCATED AT 250 WORDS)


Spontaneous peripheral arterial microembolization.

Over a seven year period 52 patients having a clinical diagnosis of spontaneous peripheral arterial microembolization were identified. Sixty-one percent of patients were female, 15% were diabetic, and 73% used tobacco chronically. A striking finding was the very high incidence of associated systemic disorders such as thrombocytosis (8), polycythemia vera (3), metastatic adenocarcinoma (3), or collagen disease requiring steroid therapy (4). Forty-nine patients had significant proximal arterial lesions as the origin of their emboli. Three patients had digital ischemia as a result of increased platelet aggregation without arterial obstruction. Forty-eight patients underwent surgical therapy. Operative mortality was 4% and overall limb salvage in survivors was 96%. The clinical syndrome of arterial microembolization may result from several pathophysiologic mechanisms including cholesterol embolization from ulcerated plaques, fibrino-platelet aggregation in patients with hematologic disorders, or dislodgement of mural thrombus in those with aneurysmal disease. We observed aortoiliac disease to be more frequent than femoral-popliteal disease, and both were amenable to surgical correction. We conclude that the genesis of arterial microembolization is multifactorial and that a variety of systemic diseases may work in concert with atherosclerotic arterial disease to produce this clinical syndrome. Prompt recognition and appropriate treatment of this disorder can yield high rates of limb salvage.


Extrahepatic portal vein aneurysm: report of a case treated by thrombectomy and aneurysmorrhaphy.

Extrahepatic portal vein aneurysm is a rare condition with only 15 cases before ours being reported in the English literature. The etiology is thought to be congenital, secondary to portal hypertension or associated with abnormal weakness of the vein wall. It often presents in conjunction with major gastrointestinal bleeding, but may occur with minimal or no symptoms. Diagnosis is made with color duplex ultrasound, computed tomographic scan, venous phase mesenteric angiography, magnetic resonance imaging, or splenoportography. Thrombosis, rupture, and pressure effects are the major complications of portal vein aneurysm. Shunting procedures are recommended in cases with portal hypertension secondary to liver disease. We report the first case treated by thrombectomy and aneurysmorrhaphy with a successful 10 year follow-up. This procedure should be considered to preserve portal vein flow when portal hypertension is absent or is secondary to the aneurysm itself.


Bypass to the lateral circumflex femoral artery.

Two patients with severe aortoiliac disease presented with total occlusion of all major femoral arteries, including the distal profunda femoris artery. Bypass to the lateral circumflex femoral artery, the most proximal branch of the profunda femoris artery, was successful in each patient. One patient had a bifurcated Dacron graft implanted from the aorta to the lateral circumflex femoral artery on each side. No sequential bypass to more distal vessels has since been necessary. The second patient underwent bypass to the lateral circumflex femoral artery from the contralateral femoral artery using saphenous vein. The procedure obviated the need to revise an above-knee amputation. The lateral circumflex femoral artery can provide suitable outflow in patients with thrombosis of the entire profunda femoris artery.


Technique and results of vascular endoscopy in arterial and venous reconstructions.

In an effort to maximize results, vascular endoscopy was used in our institution to monitor arterial and venous reconstructions. Since 1982, angioscopy was applied as a control method in 182 venous thrombectomies to treat iliofemoral thrombosis and 114 aortoiliac thromboendarterectomies. Of the cases with venous thrombectomy reviewed, 50% were incomplete by endoscopic evidence; of these, in 80% the remaining clots could be partly or completely removed. Additionally, in six patients a venous spur was found. Of 114 attempted aortoiliac thromboendarterectomies, only 91 could be completed. In the remainder, endoscopic evidence of persistent intimal flaps forced us to bypass the affected segments. With further miniaturization of the angioscopes, the method was also applied to check vessel repair on small-caliber arteries. In an initial study with 220 femorodistal bypasses we were unable to find a statistically significant difference of primary patency in grafts that were endoscopically controlled or not. In the learning phase with the in situ technique, we identified competent valve remnants in 40%, but this rate could be reduced to 12.7% with growing experience in valvulotomy. We conclude from our data that angioscopy is very helpful in assessing the morphological integrity of aortoiliac thromboendarterectomies and venous thrombectomies. The actual value in infrainguinal arterial reconstructions still remains to be proven.


Neurovascular lower extremity complications of the lithotomy position.

The lithotomy position is commonly used during the performance of a variety of abdominal and pelvic operations. Previous publications reporting complications with these operations have been largely anecdotal. We report our experience with eight patients over the past four years who have suffered serious lower extremity complications following operations in which the lithotomy position was used. The average time in the lithotomy position for our patients was 7.4 hours (range: 3.7-12 hours). The mean interval between the original operation and the secondary operation to treat the lower extremity complication was 18.9 hours (range: 2-51 hours). The average hospital length of stay for these patients, 38.4 days (range: 11-119 days), was often prolonged as a direct result of their limb complication. Serious lower extremity complications may result from operations in which the lithotomy position is used. To prevent such complications, strict attention should be paid to the positioning of the limbs in the operating room and the time in the lithotomy position should be minimized. Perioperative monitoring of the lower extremity circulation and compartment pressures are essential in these patients since early detection and treatment of these complications is the only way to prevent permanent limb injury.


Arterioureteral fistula after extended resection of pelvic tumors: report of three cases and review of the literature.

Arterioureteral fistulas are rare. Three patients with arterioureteral fistulas complicating extended resection of pelvic tumors associated with bilateral cutaneous ureterostomy in the right lower quadrant are reported. In one case, the fistula involved the left ureter, the right common iliac artery, and the inferior mesenteric artery. Pathological iliac artery, pelvic cancer, or operated ureteral stones are often incriminated in the genesis of ureteroarterial fistulas. Insertion of a ureteral catheter has been found to be the main promoting factor. The common iliac artery is involved frequently. Clinical presentation is often limited to gross hematuria, whereas complementary investigations have not proved to be sensitive. Surgical treatment is often complex, but must be undertaken early, even in the absence of absolute proof of diagnosis, in order to preclude uncontrollable massive hemorrhage.


Superior mesenteric arteriovenous fistula after ileal resection.

Postoperative superior mesenteric arteriovenous fistula is very rare. We report the case of a 55-year-old woman in whom the discovery of an abdominal bruit led to the diagnosis of superior mesenteric arteriovenous fistula seven years after ileal resection. The clinical and pathophysiological aspects, as well as the therapeutic modalities, of this rare lesion are reviewed.


Double popliteal artery of congenital origin.

An exceptional unilateral right double popliteal artery was discovered by chance. After a review of the possible causes of embryological developmental abnormalities, the most likely hypothesis is that of persistent sciatic artery.


Renal arteriovenous fistula after nephrectomy.

Postnephrectomy renal arteriovenous fistulas are rare. An arteriovenous fistula of the right renal pedicle was discovered in a 37-year-old woman who had undergone nephrectomy for renal tuberculosis nine months previously, after she had complained of dyspnea and pain in the right flank. The fistula was confirmed on arteriograms. Proximal ligation of the artery and distal ligation of the vein were followed by an uneventful recovery. Twelve months later, the patient was asymptomatic. Even though complete excision of the fistula represents the ideal treatment of this type of lesion, simple ligation can provide good results when the size of the fistula contraindicates embolization.


Rehabilitation of patients with thoracic outlet syndrome.

A series of physical therapy protocols is proposed for patients with thoracic outlet syndrome. The anatomic findings dictating certain physical therapeutic approaches are outlined. General principles of physical therapy that stem from these findings are suggested, and a specific protocol for the physical therapy regimen is given. An appropriate physical therapy program for thoracic outlet syndrome patients with symptoms of mild-to-moderate severity can avoid early surgery. Degradation of symptoms or invalidating functional compromise indicates a referral to surgery. Physical therapy cannot replace surgery in severe or complicated forms of thoracic outlet syndrome with vascular or neurologic compromise.


Transthoracic endoscopy for upper thoracic chemical sympathectomy.

Beginning in April 1989, we have performed eight upper thoracic chemical sympathectomies by transthoracic endoscopy. The indications were occlusive arterial disease in four patients and Raynaud's syndrome and palmar hyperhidrosis in two patients each. Transthoracic endoscopy was performed under general anesthesia, through the third costal interspace on the anterior mid-clavicular line. Five ml of phenol were injected into the parietal pleura covering the three proximal thoracic ganglia. The duration of thoracic drainage was 24 hours. The postoperative course was uneventful except for one case of subcutaneous emphysema and transient Horner's syndrome in three instances. There were no initial failures. Because of its simplicity and the short hospitalization period, chemical sympathectomy by transthoracic endoscopy constitutes a valuable alternative to conventional surgery. This technique is, however, limited in the case of antecedent pleuropulmonary disorders.


Molluscum contagiosum.

This in-depth review considers the known virological and molecular biological aspects of the molluscum contagiosum virus. Furthermore, the epidemiology of its infection of human skin is detailed, and the clinical, histological, and therapeutic information available at this time are cataloged. It is concluded that molluscum contagiosum has become an almost common skin disease that can prove very difficult to eradicate from an infected patient.


The natural history of recurrent oral-facial herpes simplex virus infection.

Oral-facial herpes simplex virus infection is a common, worldwide affliction on which neither public health procedures, vaccines, nor antiviral chemotherapy have yet to have a significant clinical impact. Careful examination of the pathogenesis and clinical features of this illness could lead to insights and a rationale for new and more effective preventive and therapeutic measures. The resistance of recurrent herpes simplex labialis to antiviral chemotherapy may be caused in part by inoculation of the skin simultaneously at multiple foci, such that only a few cycles of virus replication are needed before there is coalescence of the foci, destruction of the epidermis, and clinical lesion formation. Studies of herpes simplex labialis induced by ultraviolet radiation have suggested that there is a subpopulation of lesions that develop immediately after irradiation and that are refractory to chemotherapy. The difficulty finding a treatment for herpes simplex labialis may in part be methodological. Clinical trial protocols for antiviral drugs should target susceptible lesion subgroups and specific stages of the disease.


Natural history of varicella zoster virus.

The varicella zoster virus (VZV) is a herpesvirus responsible for two distinct clinical disorders, primary varicella (chickenpox) and zoster (shingles). Primary varicella is a common childhood disease in Western countries, which presents as pruritic macules, papules, vesicles, pustules, and crusts, usually on the back, chest, face, and abdomen. In immunocompetent children, chickenpox is generally a mild disease with little morbidity and rare mortality. Primary varicella is associated with more morbidity in adults. Following resolution of primary varicella, VZV persists in a latent form in dorsal ganglion cells for what is usually an extended period of time. For reasons that are still poorly understood, VZV can later start replicating in the ganglion, producing severe neuralgia and spread of the virus down the sensory nerve. Vesicles then appear on the skin in the distribution of this nerve, producing the characteristic dermatomal rash of shingles. The vesicles progress to pustules, then to crusts that eventually are lost. Scarring and changes in pigmentation can result, but the most frequent sequela of zoster is postherpetic neuralgia, which is usually most severe in the elderly. Primary varicella or herpes zoster in immunocompromised patients can sometimes involve internal organs (eg, lungs, liver, brain) resulting in high rates of morbidity and mortality. Congenital VZV infection is uncommon but can result in severe congenital malformations. A Tzanck smear can be useful to demonstrate a herpesvirus infection, but confirmation of VZV as the cause of the infection requires at least one of the following tests: culture, serology, direct immunofluorescence staining, or molecular techniques.


Treatment of postherpetic neuralgia.

Postherpetic neuralgia (PHN) is the most common and feared complication of herpes zoster. The more severe and painful the initial zoster outbreak, the more likely that PHN will develop, with elderly patients being at greatest risk. There are no proven treatments that have a large impact in reducing the risk of PHN. Tricyclic antidepressants are the mainstay of treatment for established PHN, aided by transcutaneous electrical nerve stimulation, physical therapy techniques, and cautious use of other medications. Topical agents, such as capsaicin, aspirin, and lidocaine, may soon become one of the mainstays of therapy for PHN.


Rational use of acyclovir in the treatment of mucocutaneous herpes simplex virus and varicella zoster virus infections.

The herpes family of viruses establishes latent infection in neurons and produces a spectrum of acute and recurrent clinical disease. Therapies to terminate the neurolatency or to enhance host responses are not yet available. Current therapy consists of antiviral drugs, which interfere with viral replication, can favorably alter the signs and symptoms of symptomatic disease, and act as prophylaxis against recurrent disease. Because the severity of acute and recurrent herpes group infection varies greatly between individuals, proper selection of patients to be treated with antiviral therapy is important. In general in immunocompetent patients, antiviral therapy has the greatest potential benefit for patients early in the course of primary or initial disease, or for patients with frequent and/or severe recurrent disease. Patients late in acute disease or with infrequent and/or mild recurrent disease are very unlikely to benefit from antiviral therapy. With immunocompromised patients, antiviral therapy is of the greatest potential value. By careful selection of patients, the clinician can maximize the benefits of antiviral therapy for patients with cutaneous herpes group viral infections.


Diarrhoeal diseases. Gastroenteritis and cholera epidemic, 1991.

In summary, during 1991, a substantial cholera outbreak occurred in Nepal. It presented as one of the causes of a multicausal gastroenteritis epidemic which reportedly resulted in nearly 92,000 cases and 1,800 deaths. The 1991 epidemic appeared to have been more severe with a longer duration than the epidemic which occurred in 1990. The overall case-fatality rate was 2.0%. Cholera was confirmed in 63% of faecal specimens processed, compared with 46% during the 1990 epidemic. Specimens from the first and last laboratory-confirmed cases were collected on 14 June and 26 September 1991, respectively. The presence of cholera was confirmed in all 5 development regions in the country. Contaminated public water supplies probably contributed to sustaining disease transmission, at least in urban areas.


Magnetic resonance imaging of the breast.

The diagnosis and treatment of breast cancer is dependent upon accurate depiction of the disease by diagnostic imaging. In a number of clinical situations, conventional breast imaging does not adequately address these diagnostic needs. New magnetic resonance imaging (MRI) methods developed specifically for breast diagnosis may provide the additional capability needed to fill the gap between clinical needs and the information obtained by conventional breast imaging methods. Fat-suppressed 3D MRI has demonstrated improved sensitivity over routine breast imaging methods. MRI can also be used to differentiate between certain benign but mammographically suspicious lesions and cancer. The potential clinical roles of MRI are reviewed with clinical examples. Pitfalls in the use of MRI are defined. The problems encountered with the implementation of MRI in a clinical setting are outlined and future advances predicted.


Manganese (II) N,N'-dipyridoxylethylenediamine-N,N'-diacetate 5,5'-bis(phosphate): clinical experience with a new contrast agent.

Despite the many imaging techniques available to evaluate the liver, deficiencies persist. The choice of the optimal method is still controversial, with competing issues of safety, efficacy, and cost. Numerous strategies to improve the results of liver imaging have been pursued, including the application of tissue-targeted contrast agents to magnetic resonance imaging (MRI). Manganese (II) N,N'-dipyridoxylethylenediamine-N,N'-diacetate 5,5'-bis(phosphate) (Mn-DPDP) is one of several recently developed hepatobiliary agents, targeted to functioning hepatocytes. The Mn-DPDP-enhanced MRI has demonstrated promise in the clinical trials. Contrast-to-noise measurements have shown favorable results for Mn-DPDP-enhanced MR compared to non-enhanced T1- and T2-weighted images. The ability to characterize tumors of hepatocellular origin and an improved capability for lesion detection have also been demonstrated. Furthermore, the prolonged enhancement obtained with Mn-DPDP has extended the time during which effective contrast is maintained. Importantly, no clinically significant adverse events have been demonstrated. This report will detail the clinical experience with Mn-DPDP-enhanced MRI of the abdomen.


Magnetic resonance imaging in the evaluation of cerebrospinal fluid flow abnormalities.

Phase contrast magnetic resonance imaging techniques can be used to evaluate the to-and-fro motion of cerebrospinal fluid (CSF) throughout the ventricles and subarachnoid space of the brain and spine. This CSF motion is due to transmitted cardiac pulsations from systolic expansion of the cerebral hemispheres. To cover the entire cardiac cycle, retrospective cardiac gating (rather than electrocardiographic triggering) must be used. Using this technique, it is possible to quantify CSF motion over a cardiac cycle and to distinguish normal aqueductal CSF "stroke volumes" from those seen in atrophy and shunt-responsive communicating hydrocephalus. Arachnoid cysts and other loculated CSF collections can be diagnosed using a "rebound sign" in which the motion of the CSF within the cyst is 90 degrees phase advanced over the CSF flowing around it.


Mental health: counselling sexual abuse survivors.

Some nurses are now becoming involved in helping adult survivors of child sexual abuse to overcome problems caused by an early abusive relationship. Developing a therapeutic partnership between victim and counsellor is a fundamental part of resolving such problems. Using a psychodynamic perspective, the author examines the effects of child sexual abuse on female survivors, and discusses the benefits of group therapy and individual counselling in helping the survivor to come to terms with the abuse.


An alternative to urinary conduit.

The author outlines the procedures involved in creating a Mitrofanoff pouch as an alternative to urinary conduit. Patients who have such a procedure must learn to alter their lifestyles and acquire skills such as self-catheterisation, but early results suggest that they find the procedure acceptable and preferable to other options.


Rehabilitation of muscle function. Part 1.

This article, which develops the concepts introduced in the authors' paper in last week's edition (1), is the first of two which review and summarise recent studies describing techniques to test the hypothesis that uniform frequency stimulation of skeletal muscle deprives the muscle of the type of signals that are necessary for rapid, appropriate and effective adaptation. Next week, clinical trials which have tested this hypothesis will be described, and the implications of the results for nurses involved in rehabilitation work discussed; Part 1 sets out the methodology of extracting the firing patterns of single motor units from a fatiguing muscle.


Testing renal patients for HIV: guidelines.

These guidelines for the testing of renal patients have been produced by the RCN Dialysis and Transplant Nurses Forum following a questionnaire sent to 61 renal units in the UK in 1988. Questions were asked relating to the current practice of testing patients for HIV within the renal population. The huge diversity of practice clearly demonstrated a fundamental lack of awareness of the ethical issues that are involved.


Aggression: therapeutic response to verbal abuse.

Increasing numbers of nurses in a variety of settings have to deal with physical and verbal aggression meted out by their patients. This article concentrates on suitable therapeutic responses to verbal abuse, and urges the nurse to consider aggression in a wider context, looking at the predisposing factors and methods to defuse potentially violent situations. The author stresses that self-evaluation is crucial if skills are to be learned and applied to subsequent episodes.


Rehabilitation of muscle function. Part 2.

This article describes the utilisation of a physiologically based research technique developed to facilitate the nursing care of patients with skeletal muscle wasting. The technique, which involved electrotherapeutic stimulation to the first dorsal interosseous muscle of a group of arthritic patients, demonstrates that patterned neuromuscular stimulation of skeletal muscle can have enormously beneficial effects in preserving and regenerating skeletal muscle. The reasons for the muscle wasting, and the subsequent vicious spiral of immobility, were reviewed in Part 1 (1), and both articles build on the concepts described in a previous paper published in Nursing Standard (2).


Occupational health: developing safe handling policies.

This article is based on a paper given by the author at the Royal College of Nursing's Congress in April 1992, and is the first John Goodland Memorial Lecture. It examines the need for safe handling policies, and highlights the essential components of any new policy. With legislative changes due to come into force on December 31 1992, managers and staff are urged to be aware of the impact of safe handling training and how it can affect care delivery.


Oncology: chemotherapy for elderly people.

Elderly people form a large proportion of cancer patients. This has implications for cancer care, in that age is a substantial risk factor in developing cancer. In spite of efforts to reduce cancer mortality through health education and screening, cancer rates are likely to increase in proportion to the ageing population. It has been suggested that health care professionals generally view elderly people in a negative fashion, which influences the care that these individuals receive. At present, there is a scarcity of information on the nature of cancer in elderly people, their tolerance to cytotoxic treatment, and specific age-related problems. Knowledge in all these areas remains fragmented and the research data conflicting. The nurse plays an important role in assessing and monitoring the impact of cytotoxic chemotherapy treatment. It is, therefore, imperative for cancer nurses to develop specialist knowledge in this area to enable them to understand the effect cytotoxic chemotherapy treatments have on elderly people.


Mental health. Rehabilitation: a progressive approach.

For clients who have depended heavily on psychiatric services, or who have had lengthy admissions to hospital, the move to independent living can be a traumatic and difficult time if adequate support is not available. The author describes a rehabilitation unit for such clients, where staff aim to help them reach realistic decisions about their futures in a supportive environment.


Nurse education in the Sultanate of Oman.

The quality of health care in the Sultanate of Oman has improved considerably over the past 20 years. Nurse education has developed accordingly with input from British nurses, many of whom leave the United Kingdom to work there every year. The author describes how nurse education has developed in the Sultanate and how, in spite of the influence and values of Western countries, the importance of the indigenous culture is not ignored.


Occupational health: the nurse's role in workplace assessment.

In September 1991, the Health & Safety Executive (HSE) launched its biggest ever national awareness campaign relating to health at work. Called 'Lighten the Load', the campaign aims to raise awareness of work-related musculoskeletal disorders and encourage employers to reduce the frequency with which they occur. Occupational health nurses are ideally placed to play a major and active part in the campaign and assist in increasing awareness in both employers and the workforce.


Acholeplasma multilocale sp. nov., isolated from a horse and a rabbit.

Acholeplasma strains were isolated from the nasopharynx of a horse (strain PN525T [T = type strain]) and the feces of a rabbit (strain B1). One clone of strain PN525T and one clone of strain B1 were examined in detail. These clones were indistinguishable from each other and were serologically distinct from the previously described Acholeplasma and Mycoplasma spp. The strains had the following properties: guanine-plus-cytosine content of 31 mol%; sterol was not required for growth, which occurred under both aerobic and anaerobic conditions; glucose was metabolized; and arginine was hydrolyzed. Strain PN525 (= NCTC 11723) is the type strain of a new species, Acholeplasma multilocale.


Mycoplasma simbae sp. nov., Mycoplasma leopharyngis sp. nov., and Mycoplasma leocaptivus sp. nov., isolated from lions.

Mycoplasmas isolated from the throats of lions were shown to belong to three serotypes, all of which were serologically distinct from the previously recognized Mycoplasma and Acholeplasma spp. Eight mycoplasma colonies were cloned, including one from a leopard (strain LP), and were examined in detail for morphology, growth, and biochemical characteristics. The strains had the following properties: guanine-plus-cytosine contents of 37 mol% (strain LXT [T = type strain]), 28 mol% (strain LL2T), and 27 mol% (strain 3L2T) and a requirement for sterol. Strain 3L2T metabolized glucose, which was not metabolized by strains LXT and LL2T. Arginine and urea were not hydrolyzed. Strain LX (= NCTC 11724) is the type strain of a new species, Mycoplasma simbae; strain LL2 (= NCTC 11725) is the type strain of a second new species, Mycoplasma leopharyngis; and strain 3L2 (= NCTC 11726) is the type strain of a third new species, Mycoplasma leocaptivus.


Mycobacterium alvei sp. nov.

A new species of rapidly growing, nonphotochromogenic mycobacteria, Mycobacterium alvei, is described. The inclusion of this organism in the genus Mycobacterium is based on its acid fastness, its mycolate pattern, and its G + C content. A study of six strains showed that they form a homogeneous group with an internal phenotypic similarity value of 97 +/- 2.22%. DNA relatedness studies showed that the six M. alvei strains which we studied form a single DNA hybridization group which is less than 49% related to 14 other species of the genus Mycobacterium; the deltaTm values determined for the strains which exhibited higher levels of DNA homology were all greater than 7.9 degrees C. A lipid analysis showed that tuberculostearic acid was present. Docosanoic and tetracosanoic acid methyl esters were detected as mycolic acid cleavage products. All six isolates which we tested contained alpha-mycolic acids and relatively large amounts of a new kind of mycolic acid containing a methoxy group of omega-1 position, a characteristic that has not been described previously in mycobacteria. Strain CR-21 is the type strain; a culture of this strain has been deposited in the Collection Nationale de Cultures de Microorganismes de l'Institut Pasteur, Paris, France, as strain CIP 103464.


Emended descriptions of Prevotella denticola, Prevotella loescheii, Prevotella veroralis, and Prevotella melaninogenica.

During studies of human periodontal disease, a number of bacterial strains were encountered that, on the basis of results of standard biochemical tests, appeared to be Prevotella buccalis, Prevotella denticola, Prevotella melaninogenica, or Prevotella loescheii. However, use of the standard biochemical tests, cellular fatty acid analyses, and the polyacrylamide gel electrophoresis patterns of soluble proteins resulted in conflicting identifications of these strains. The results of tests for cellobiose fermentation, inulin fermentation, and pigment production were responsible for most of the discordant results. Cellular fatty acid analyses in which the Microbial Identification System was used did not differentiate these strains from validly described species, even though separate library entries were created for them. DNA reassociation determinations in which the S1 nuclease procedure was used showed that cellobiose fermentation and pigment production are variable among strains of P. melaninogenica and P. denticola and that fermentation of xylan is not a reliable characteristic for differentiating P. buccalis from Prevotella veroralis. In contrast to previous indications, most strains of P. veroralis do not ferment xylan. These species can be differentiated by DNA-DNA reassociation and by cellular fatty acid analysis, using the Microbial Identification System, but differentiation by currently described phenotypic characteristics is not reliable. Similarly, P. loescheii and the genetically distinct (but closely related) D1C-20 group cannot be distinguished reliably from each other or from P. veroralis, P. denticola, and P. melaninogenica on the basis of currently described phenotypic tests other than cellular fatty acid composition or, for some species, electrophoretic patterns of soluble whole-cell proteins.


Biochemical and chemical studies on strains designated Prevotella intermedia and proposal of a new pigmented species, Prevotella nigrescens sp. nov.

A total of 31 strains of Prevotella intermedia were subjected to DNA-DNA hybridization and were characterized by performing physiological tests and by performing a multilocus enzyme analysis, using malate dehydrogenase and glutamate dehydrogenase. All of the strains assigned to P. intermedia fermented glucose and sucrose, hydrolyzed starch but not esculin, and produced indole, acetic, isobutyric, isovaleric, and succinic acids as metabolic end products. The results of DNA reassociation experiments performed with the reference probe permitted separation of the strains into two well-defined homology groups. In addition, strains with DNAs that hybridized with DNA from strain ATCC 25611T (T = type strain) had high levels of peptidase activity and cleaved lipid substrates (4-methylumbelliferyl laurate and 4-methylumbellifelyl elaidate). Multilocus enzyme electrophoresis revealed two electromorphic profiles, one characteristic of strain ATCC 25611T and the other characteristic of strain ATCC 33563T. We propose that a new species, Prevotella nigrescens, should be created for the genetically distinct group of strains that hybridized with strain ATCC 33563T. Strain ATCC 33563 is designated the type strain of P. nigrescens.


Staphylococcus piscifermentans sp. nov., from fermented fish in Thailand.

New coagulase-negative staphylococci were isolated from fermented fish in Thailand. These organisms were differentiated from other Staphylococcus species on the basis of DNA relatedness and biochemical characteristics. Staphylococcus piscifermentans sp. nov. is described, and the type strain is strain SK03 (= NRIC 1817 = JCM 6057 = TISTR 824).


Acholeplasma cavigenitalium sp. nov., isolated from the vagina of guinea pigs.

A mollicutes isolated from a guinea pig vagina was shown to be serologically distinct from previously recognized Mycoplasma and Acholeplasma species. Colonies isolated from 10 different guinea pigs were cloned and examined in detail. These strains were closely related and had the following properties: guanine-plus-cytosine content of 36 mol%, no requirement for sterol, and aerobic growth. Glucose was not metabolized, and arginine and urea were not hydrolyzed. Strain GP3 (= NCTC 11727) is the type strain of a new species, Acholeplasma cavigenitalium.


Relationships between members of the Mycoplasma mycoides cluster as shown by DNA probes and sequence analysis.

A gene probe, CAP-21, which demonstrated interrelationships between the members of the Mycoplasma mycoides cluster was developed. The probe easily differentiated mycoplasmas in this cluster by clear and predictable hybridization patterns in Southern blots and separated the cluster into four groups. Strains of M. mycoides subsp. mycoides which were capable of causing contagious bovine pleuropneumonia composed one group. Strains of M. mycoides subsp. mycoides which did not cause contagious bovine pleuropneumonia together with strains of M. mycoides subsp. capri composed the second group. Mycoplasma capricolum and the F38 mycoplasmas formed a third group, while the bovine group 7 mycoplasmas composed a separate, fourth group. Further support for the above grouping of the cluster was obtained when amplified DNA analogous to the probe from one representative strain of each of the cluster members was sequenced and these data were used to construct a phylogenic tree. Contagious caprine pleuropneumonia is recognized as an important disease, and the etiological agent of this disease is now known to be the F38 mycoplasma. The CAP-21 probe did not differentiate between M. capricolum and the closely related F38 mycoplasma. A second probe, F38-12, which was capable of distinguishing these two mycoplasmas was made.


Three new species of the genus Peptostreptococcus isolated from humans: Peptostreptococcus vaginalis sp. nov., Peptostreptococcus lacrimalis sp. nov., and Peptostreptococcus lactolyticus sp. nov.

We describe three new species of the genus Peptostreptococcus which were isolated from human specimens and were tentatively identified as Peptostreptococcus prevotii. These three organisms were not homologous with previously described type strains of the genus Peptostreptococcus. A total of 12 strains that were identified biochemically as P. prevotii were divided into five independent DNA similarity groups; 10 of these strains were divided into three similarity groups which exhibited significant phenotypic differences from previously described species. Therefore, we propose the following new species: Peptostreptococcus vaginalis for group 1 strains, Peptostreptococcus lacrimalis for group 2 strains, and Peptostreptococcus lactolyticus for group 3 strains. The type strain of P. vaginalis is strain GIFU 12669 (= JCM 8138), the type strain of P. lacrimalis is strain GIFU 7667 (= JCM 8139), and the type strain of P. lactolyticus is strain GIFU 8586 (= JCM 8140).


Recognition of Morganella subspecies, with proposal of Morganella morganii subsp. morganii subsp. nov. and Morganella morganii subsp. sibonii subsp. nov.

The genus name Morganella was established within the family Enterobacteriaceae in 1978. Morganella morganii is the only species described thus far within this genus, and the name M. morganii has been accepted by usage in the scientific community for strains previously known as Proteus morganii. M. morganii isolates differ in their abilities to ferment trehalose and exhibit variable lysine and ornithine decarboxylase patterns, emphasizing the phenotypic heterogeneity within this species. Previous genetic studies failed to reveal separate entities within the genus Morganella. We observed some trehalose-fermenting strains with different lysine and ornithine decarboxylase patterns. Two strains were lysine and ornithine positive, 3 were lysine positive and ornithine negative, and 29 were lysine negative and ornithine positive. These strains and 25 non-trehalose-fermenting strains with different lysine and ornithine decarboxylase patterns were investigated. DNA-DNA hybridization studies and phenotypic characterizations revealed that M. morganii can be separated into three DNA relatedness groups and seven biogroups. Strains from DNA relatedness group 1 were trehalose negative, and strains from DNA relatedness groups 2 and 3 were trehalose positive. One biogroup from DNA relatedness group 2 was phenotypically indistinguishable from DNA relatedness group 3. On the basis of these studies, we propose that M. morganii be subdivided into M. morganii subsp. morganii (type strain ATCC 25830) containing biogroups A, B, C, and D (DNA relatedness group 1) and M. morganii subsp. sibonii (type strain 8103-85; = ATCC 49948) containing biogroups E, F, and G (DNA relatedness groups 2 and 3).


Isolation and characterization of Shewanella alga from human clinical specimens and emendation of the description of S. alga Simidu et al., 1990, 335.

Genetic and phenotypic studies on the strains biochemically identified as Shewanella putrefaciens, which had a G+C content ranging from 52 to 54 mol% were conducted. The moles percent G+C of the type strain of S. putrefaciens is 46. Surprisingly, DNA homology experiments revealed that all these strains are genetically related to Shewanella alga (which was reported to produce tetrodotoxin), not to the type strain of S. putrefaciens. In this study, we reidentified clinical strains of S. putrefaciens which have a high range of moles percent G+C, as does S. alga. We also characterized the reidentified strains and found that the original description of S. alga (U. Simidu, K. Kita-Tsukamoto, T. Yasumoto, and M. Yotsu, Int. J. Syst. Bacteriol. 40:331-336, 1990) is insufficient to identify this strain. An emended description of S. alga is given.


Identity of V factor in culture medium used for prior growth of two strains of Staphylococcus aureus.

Staphylococcus aureus ATCC 12598 and ATCC 25923 were starved of pyridine nucleotides and precursors and then grown in a semidefined medium containing [carbonyl-14C]nicotinamide. Samples of medium from late-exponential-phase and stationary-phase cultures were analyzed for 14C-metabolites. In all cases, V factor was present primarily as NAD.


Variability of serum levels for three oral 8-methoxypsoralen brands.

We conducted a pilot study to investigate the serum level patterns of 3 commercial and internationally introduced 8-methoxypsoralen (8-MOP) preparations in 9 patients for their bioequivalence and registered the interindividual variability of serum levels over 8 h after intake of 30 mg 8-MOP equivalent doses. On average, the highest serum levels (Cmax 120.1, range 235-61 ng.ml-1) were reached as early as 0.5-1 h after ingestion of Geroxalen soft gelatin capsules, whereas lower serum levels were seen after intake of the Oxsoralen hard gelatin capsules (Cmax 82.3, range 154-47 ng.ml-1) and the Mopsoralen tablets (Cmax 81.3, range 172-26 ng.ml-1). The importance of 8-MOP serum level determination for better and efficient PUVA therapy is discussed.


Ultraviolet B dose-dependent inflammation in humans: a reflectance spectroscopic and laser Doppler flowmetric study using topical pharmacologic antagonists on irradiated skin.

Normal skin responds acutely to ultraviolet (UV) light exposure with complex inflammatory mechanisms. In the present study UVB irradiation ranging from subclinical erythema doses to twice the minimal erythema dose (24 mJ/cm2 to 96 mJ/cm2) was delivered to the skin of 8 volunteers. Pre-irradiated sites were immediately afterwards exposed to a 24-h occlusive patch containing 1 of 4 anti-inflammatory agents or vehicle control. The resultant change in erythema (vascular reaction) was measured objectively using laser Doppler flowmetry (LDF) and reflectance spectroscopy (RS). The 4 anti-inflammatory compounds reduced the UVB-induced vascular reactions in different and dose-dependent ways. Betamethasone-17-valerate and diphenhydramine were most effective at the 24 mJ/cm2 dose site and indomethacin and acetylsalicylic acid were more effective at sites > or = 48 mJ/cm2. Ranking the reduction in oxygenized hemoglobin (OH) content was as follows: betamethasone-17-valerate (OH reduction = 37.4%) > indomethacin (OH reduction = 21.5%) > acetylsalicylic acid (ASA) (OH decrease = 21.0%) > diphenhydramine (OH reduction = 18.4%). Using LDF, the total ranking of the cutaneous blood flow (BF) reduction was: indomethacin (BF reduction = 39.7%) > betamethasone-17-valerate (BF reduction = 32.7%) > acetylsalicylic acid (BF decrease = 17.5%) > diphenhydramine (BF reduction = 12.3%). Diphenhydramine significantly reduced erythema only at the lowest irradiation dose (24 mJ/cm2) and the decrease in OH was associated with an increased amount of deoxygenized hemoglobin (DOH). A similar slight venous dilatation was present at acetylsalicylic acid-exposed sites.(ABSTRACT TRUNCATED AT 250 WORDS)


The relative importance of the components used for ultraviolet A protection in broad-spectrum sunscreens.

The need for effective ultraviolet A (UVA) protection is increasing. Broad-spectrum sunscreens are being used to protect the skin against aging and in the treatment of photodermatoses, where UVA protection can be vital. They are also used by patients taking photosensitizing drugs, such as 8-methoxypsoralen, to protect their skin against solar UVA. This raises the question of what components in broad-spectrum sunscreens are the most necessary for optimal UVA protection. In the present study, the components that can be used are compared and evaluated using an animal method with the inhibition of skin edema induced by 8-methoxypsoralen plus UVA as the biological end point. The results of this method indicate that powders do not provide any significant UVA protection. This could be due to the use of 8-methoxypsoralen in the test so that particularly the shorter UVA range is evaluated. Powders reflect mainly the longer UVA wavelengths. The UVA protection as measured with this method seems to be similar for the benzophenone derivative and for the dibenzoylmethane derivative. The UVA protection factors obtained are compared with those obtained in human skin using phototoxic erythema and UVA-induced tanning as parameters.


Immunomodulatory effects of AS101 on interleukin-2 production and T-lymphocyte function of lymphocytes treated with psoralens and ultraviolet A.

This study tested the immunomodulatory effects of AS101, a synthetic organotellurium compound, on interleukin (IL-2) production and functional activity of normal human lymphocytes. Normal human lymphocytes were treated in vitro with 8-methoxypsoralen alone, ultraviolet A (UVA) and psoralen plus UVA (PUVA) as well as with a combination of AS101 + phytohaemagglutinin (PHA)+phorbol myristate acetate (PMA) and the above-mentioned treatments. Following treatment IL-2 production, free IL-2 receptor (IL-2R), the ability of lymphocytes to induce a local graft-versus-host reaction (GVHR) and the ability of separated CD4 cells to induce help were tested. 8-Methoxypsoralen alone did not significantly affect either cell proliferation or IL-2 production or functional activity. However, UVA and PUVA had a high inhibitory effect on cell proliferation, IL-2 production, IL-2R release and the functional activity of T- and T-helper lymphocytes. In the present study, the addition of AS101 and PMA serve to restore the impaired IL-2 production, T- and T-helper lymphocyte functional activity, but not the IL-2R release. AS101 alone without PMA was also effective in restoring GVHR and helper activity of CD4 lymphocytes, without affecting cell proliferation.


Liquid formulations of 8-methoxypsoralen (8-MOP) and 5-MOP: a prospective double-blind crossover assessment of acute non-phototoxic adverse effects.

Thirty-nine patients with psoriasis undergoing PUVA participated in a prospective double-blind study of acute non-phototoxic adverse effects comparing the liquid formulations of 8-methoxypsoralen (0.6 mg/kg) and 5-methoxypsoralen (1.2 mg/kg). A much higher number of patients experienced nausea (8-MOP = 51.3%, 5-MOP = 7.7%) and pruritus (8-MOP = 71.8%, 5-MOP = 43.6%) than has been reported for crystalline tablets. No attempt was made to compare therapeutic efficacy between liquid and crystalline tablet formulations or between 8-MOP and 5-MOP, which both appeared to be effective. The high incidence of adverse effects suggests that current dosage recommendations be reviewed.


Influence of ultraviolet A on scheduled and unscheduled DNA synthesis by ultraviolet B.

After irradiating mouse epidermis in vivo with ultraviolet radiation (UV), autoradiography using 3H-thymidine was performed to study the effects of UV on scheduled and unscheduled DNA synthesis during a 7 day-period. Suppression of scheduled DNA synthesis by 100 mJ/cm2 of UVB was continued for about 24 h and induction of unscheduled DNA synthesis by 100 mJ/cm2 of UVB for about 6 h after irradiation. It was also confirmed that UVA induced DNA damage if a dose of UVA over 30 J/cm2 was used. When UVA was applied 1 h before UVB irradiation, a significant increase in sparsely labeled cells (SLC) was observed and the numbers of SLC increased in proportion to the total dosage of UV. So it was confirmed that UVA preirradiation enhanced DNA damage by UVB.


Effect of psoralen and ultraviolet A on platelet functioning: an in vitro and in vivo study.

We investigated possible alterations induced by psoralen and ultraviolet A radiation (PUVA) on platelet function both in vitro and in vivo. In vitro, using conventional aggregometry and adenosine diphosphate (ADP), collagen, ristocetin and arachidonic acid as aggregating agents, platelet aggregation was determined on platelet-rich plasma (PRP) from normal subjects at basal conditions and following the addition of increasing concentrations of 8-methoxypsoralen (8-MOP) with and without exposure to ultraviolet A (UVA) light (5 J/cm2) and compared with UVA light exposure alone. At basal conditions and following exposure to UVA light alone, no changes in the normal platelet aggregation patterns were observed. Exposure to UVA light of PRP containing 8-MOP also demonstrated no abnormality in the platelet aggregation patterns at 8-MOP concentrations of 200 ng/ml. However, abnormal platelet aggregation as a response to ADP and collagen was observed at higher concentrations of 8-MOP, which was augmented upon exposure to UVA light. In vivo, platelet aggregometry was performed on PRP from 4 patients submitted to PUVA treatment at basal conditions, 2.5 h after oral ingestion of 8-MOP (0.6-0.8 mg/kg) and after 4 PUVA sessions. No patient showed modification of the platelet aggregation profile after either 8-MOP ingestion or PUVA treatment. Our study shows that 8-MOP at high concentrations in vitro impairs platelet aggregation by ADP and collagen augmented by UVA light exposure, but PUVA therapy causes no detectable abnormality in platelet function in vivo.


Solar ultraviolet (UV) radiation and UV doses received by patients during four-week climate therapy periods in the Canary Islands.

The ultraviolet (UV) radiation doses received by 270 psoriasis patients were studied during 4-week climate therapy periods in November, March or April in the Canary Islands. The daily total solar UV radiation (ambient radiation load, ARL) was measured using frequent readings with a Robertson-Berger sunburning ultraviolet (SUV) meter. A daily personal radiation load (PRL) was calculated for each patient, using sun exposure diary data. To measure the cumulative UV exposure of particular skin sites (skin site dose, SSD), 10 patients wore polysulphone UV dosimeters. The daily ambient radiation load (ARL) ranged from 2.9 to 8.9 erythemal units (EU); the cumulative ARL for a 4-week treatment period was 182.6 EU. The mean daily personal radiation load (PRL), calculated separately for each week of the treatment period, was from 2.5 to 5.6 EU; the mean total 4-week PRL was 118.0 EU, being about 65% of the ARL. The 4-week cumulative skin site dose (SSD) varied between 22.2 and 63.3% (mean 41.2%) of the corresponding personal radiation load (PRL).


The distribution of alpha 6 beta 4 integrins in lesional and non-lesional skin in bullous pemphigoid.

The alpha 6 beta 4 integrin is associated ultrastructurally with the hemidesmosomes of the basal keratinocytes and with the bullous pemphigoid antigen (BPA), suggesting an important role in adhesion of epidermal cells to the basement membrane. Using an immunofluorescence technique with chain-specific monoclonal antibodies to the alpha and beta subunits we have investigated the distribution of the alpha 6 beta 4 integrin in normal skin (n = 3) and in BP skin (uninvolved, perilesional and lesional) [n = 11]). The findings have been compared with other types of subepidermal blisters and with normal skin split by chemical means (n = 2) and by suction (n = 2). The distribution of alpha 6 beta 4 integrin was compared with that of bullous pemphigoid antigen (BPA) and with other basement membrane zone (BMZ) macromolecules, laminin, collagen type IV, collagen type VII and the BM600 antigen. In uninvolved, perilesional and early pre-blistered lesional BP skin the distribution of both the alpha 6 and beta 4 integrin subunits, BPA laminin, collagen types IV and VII and the BM600 antigen was identical to normal skin, i.e. a linear band in the BMZ. Within BP blisters, both alpha 6 and beta 4 integrin subunits and BPA were absent, except in two blisters in which the integrin expression was retained in the blister roof, despite loss of BPA. The other BMZ components were expressed on the blister floor.(ABSTRACT TRUNCATED AT 250 WORDS)


Ultrastructural immunogold studies in two cases of linear IgA dermatosis. Are there two distinct types of this disease?

It has been suggested that patients with homogeneous linear IgA deposits at the basement membrane zone constitute a distinct bullous disorder called linear IgA dermatosis (LAD) of adults or children. The results of the present ultrastructural immunogold study in two patients with LAD suggest that LAD is not a single disease entity. LAD in a 10-year-old girl was found to be ultrastructurally similar to an IgA-type pemphigoid. IgA was detected in the uppermost lamina lucida underlying the basal cell plasma membrane. In a second patient, an 86-year-old man, IgA deposits were present within the lamina densa and the anchoring plaques. The distribution of IgA in this patient was ultrastructurally identical with that of IgG in epidermolysis bullosa acquisita skin and with that of the non-collagenous globular terminus of collagen VII within the basement membrane zone of normal skin. By using the immunogold technique, we could distinguish two distinct types of LAD according to the IgA binding sites in the diseased skin. We suggest that different labelling patterns may correspond to different clinical pictures.


Failure to demonstrate the true resection margins of excised skin tumours: a case for routine marking.

A solution of silver nitrate in methanol was used to assess the demonstration of the true surgical excision margin at histology of 100 skin excisions for basal cell carcinoma. In 15% of cases the true margin was not presented and deeper sections were required. The findings highlight the need for routine marking of excision specimens of neoplastic skin lesions to prevent incorrect diagnosis of incomplete excision based on a false resection margin.


Dynamic hepatic scintigraphy in the screening of psoriatic patients for methotrexate-induced hepatotoxicity.

We report the use of dynamic hepatic scintigraphy in the assessment of the hepatic status of psoriatic patients before and during methotrexate therapy. Eighty-seven paired dynamic scans and percutaneous liver biopsies were performed in 63 patients. The liver biopsies were graded according to Warin et al. with fibrosis of grade 2 or worse being a strong indication for withdrawal of methotrexate. The sensitivity of dynamic hepatic scintigraphy in detecting fibrosis of grade 2 or worse was 83.3% and the specificity was 81.5%. The predictive value of a normal scan for fibrosis of grade 0-1 was high (98.5%) although the predictive value of an abnormal scan for fibrosis of grade 2 or worse was low (25%). Dynamic hepatic scintigraphy may therefore offer a means to reduce the number of liver biopsies necessary in patients receiving methotrexate for psoriasis.


The phenotype of Darier's disease: penetrance and expressivity in adults and children.

The prevalence, pattern of inheritance, and phenotype of Darier's disease was examined in a cross-sectional study of cases in north-east England. Seventy-five cases, representing a local prevalence of at least 1:36,000, were identified and examined. Forty-two cases were known to dermatologists, and 33 were identified in the course of the study: 60 were adults (above the age of 20) and 15 were children. In nine families, 66 of 136 adults with an affected parent were known to be affected, indicating complete penetrance of an autosomal dominant gene. eighteen individuals gave no family history, but seven of these were found to be members of affected kindreds and five obligate carriers examined all proved to have evidence of the disease. In other 'new' cases, including several whose parents were examined and confirmed to be normal, no relationship to other cases was found. These cases probably represent new mutations or non-paternity rather than incomplete penetrance. All but one adult case had the typical rash, but it was milder in women; 16/18 adults who had not presented to dermatologists were female. Diagnostic nail lesions were found in 59 (99%), palmar pits and keratoses in 57 (95%), and acrokeratosis verruciformis in 44 (73%). In 15 young cases (aged 5-18) with one or more diagnostic features, the rash was found in only four (27%), nail lesions in nine (60%), palmar pits in eight (53%), and acrokeratoses in ten (67%). The minor lesions were often subtle but were more consistent early evidence of disease than the rash, and even in the absence of a rash gene penetrance may be complete by the age of 10.


The influence of daily dish-washing with synthetic detergent on human skin.

The effects of regular dish-washing on the stratum corneum barrier function, as determined by transepidermal water loss (TEWL), and objective and subjective skin parameters, were investigated in a 'use test' performed by 18 healthy volunteers. Hands were soaked in a 0.05% solution of a commercial dish-washing product (three times/day, for 15 min, at 37 degrees C) over a period of 3 weeks; one hand was unprotected and the other was protected with a commercial rubber glove. TEWL increased in 13/18 volunteers by more than 25% above baseline on exposed hands within the first 2 weeks of the study. Objective skin signs (erythema, scaling, fissures) and subjective symptoms (itching, dryness, smarting) occurred almost exclusively in subjects with substantial TEWL increases and were most prominent 1-2 weeks following peak TEWL values. There was a highly significant correlation between cumulative relative symptom scores and TEWL changes. TEWL increase and symptom scores were not correlated with a history of inhalant allergy and/or elevated serum IgE levels. Three volunteers, who had shown the highest increase of TEWL values and the most intense clinical reactions to the detergent were subjected to a control experiment in which one hand was soaked in warm tap-water following the same experimental protocol. No significant effects on TEWL values or skin symptoms were observed. We conclude that regular exposure to low concentrations of detergents as used for dish-washing is capable of inducing skin lesions in a substantial proportion of individuals.


Cutaneous manifestations of the eosinophilia-myalgia syndrome.

We report the cutaneous manifestations of the eosinophilia-myalgia syndrome in 10 patients, with specific reference to their clinical course, histopathological features, and immunogenetic studies. Cutaneous manifestations could be classified into three groups: morphoea-like sclerosis, urticarial and papular lesions, and generalized sclerosis. Despite this polymorphic clinical presentation, the histopathological abnormalities in all cases were strikingly similar, and consisted of superficial and deep perivascular lymphocytic dermal infiltrates, mucin deposition, and fascial inflammation (often in the absence of sclerosis). Immunoperoxidase studies revealed increased numbers of factor XIIIa- and MAC 387-positive cells in the inflammatory infiltrate. Immunogenetic studies demonstrated that 77% (7/9) of patients possessed the HLA-DR3 or HLA-DR4 phenotypes. Mean follow-up of 24 months after discontinuation of L-tryptophan revealed the presence of persistent severe disabling disease in 30% of patients.


A portable pulsed electromagnetic field (PEMF) device to enhance healing of recalcitrant venous ulcers: a double-blind, placebo-controlled clinical trial.

A prospective, randomized, double-blind, placebo-controlled multicentre study assessed the clinical efficacy and safety of pulsed electromagnetic limb ulcer therapy (PELUT) in the healing of recalcitrant, predominantly venous leg ulcers. The portable device was used at home for 3 h daily during this 8-week clinical trial as an adjunct to a wound dressing. Wound surface area, ulcer depth and pain intensity were assessed at weeks 0, 4 and 8. At week 8 the active group had a 47.7% decrease in wound surface area vs. a 42.3% increase for placebo (P < 0.0002). Investigators' global evaluations indicated that 50% of the ulcers in the active group healed or markedly improved vs. 0% in the placebo group, and 0% of the active group worsened vs. 54% of the placebo group (P < 0.001). Significant decreases in wound depth (P < 0.04) and pain intensity (P < 0.04) favouring the active group were seen. Patients whose ulcers improved significantly after 8 weeks were permitted to continue double-blind therapy for an additional 4 weeks. Eleven active and one placebo patient continued therapy until week 12, with the active treatment group continuing to show improvement. There were no reports of adverse events attributable to this device. We conclude that the PELUT device is a safe and effective adjunct to non-surgical therapy for recalcitrant venous leg ulcers.


Roxithromycin versus penicillin in the treatment of erysipelas in adults: a comparative study.

A prospective, randomized, multicentre trial was conducted to evaluate the efficacy and safety of roxithromycin (150 mg b.i.d. orally) and penicillin (2.5 MU x 8 daily intravenously, then 6 MU daily orally) in the treatment of hospitalized adult patients with erysipelas. Seventy-two patients entered the study. Thirty-one patients in the roxithromycin group and 38 patients in the penicillin group completed the trial. The overall efficacy rates (cure without additional antibiotics) were 84% (26/31) in the roxithromycin group and 76% (29/38) in the penicillin group (P = 0.43). No side-effects were observed in the roxithromycin-treated patients whereas rashes occurred in two cases in the penicillin group, leading to exclusion from the study. Oral roxithromycin can thus be considered an effective and well-tolerated treatment for erysipelas in adult hospitalized patients.


Extensive and fatal basal cell carcinoma: a report of three cases.

Three cases of basal cell carcinoma (BCC) with extensive invasion are described. The first two patients had meningeal and cerebral involvement with exposure of their dural meninges following full thickness skull erosion. The third patient had bilateral orbital and optic nerve involvement resulting in complete blindness. All three patients subsequently died from their disease.


An acantholytic dyskeratotic epidermal naevus with other features of Darier's disease on the same side of the body.

Many epidermal naevi with the histology of Darier's disease have been reported. In the absence of associated features of Darier's disease, they cannot be assumed to have a common pathogenesis with it, and it has been suggested that they are better classified as acantholytic dyskeratotic epidermal naevi rather than naevoid Darier's disease. We describe a patient with such a naevus who had typical nail and palmar changes of Darier's disease on the same side of the body. We suggest that in at least some cases the naevus has the same genetic defect(s) as generalized Darier's disease, and discuss the possibility that a patient with such a naevus could occasionally transmit Darier's disease to an offspring.


Epidermolysis bullosa acquisita with oesophageal stenosis.

Epidermolysis bullosa acquisita (EBA) is a rare acquired subepidermal blistering disorder associated with autoimmunity to type VII collagen. Although the full clinical spectrum of EBA is still being defined, it is now known that EBA has greater clinical heterogeneity than previously suggested. We describe a patient with EBA which closely approximated the severity of the recessive form of dystrophic epidermolysis bullosa.


Multiple xanthogranulomas in an adult: case report and literature review.

An otherwise healthy 30-year-old male developed multiple xanthogranulomas over a 1-year period. A review of the literature on adult xanthogranulomas and a tabulated outline of the differential diagnosis is presented.


Cutaneous granulocytic sarcoma (chloroma) presenting as the first sign of relapse following autologous bone marrow transplantation for acute myeloid leukaemia.

A 25-year-old man suffering from acute myeloid leukaemia developed a solitary lesion on the upper abdominal wall 6 months after receiving an autologous bone marrow transplant. The lesion was a chloroma and proved to be the only evidence of clinical relapse. This is the first reported case of this rare condition occurring following bone marrow transplantation.


Vitamin D analogues and psoriasis.

Topical vitamin D analogues offer a new, effective, more convenient and generally well-tolerated option for the treatment of psoriasis. Only psoriasis vulgaris has been intensively studied, but other forms of the disease may also respond. Both calcitriol and calcipotriol have been shown to be effective in numerous clinical trials, and the latter has compared well with betamethasone valerate and short-contact dithranol in controlled studies. Their mechanism of action is not yet fully understood and may prove complex. The most important effect may be a direct regulation of keratinocyte proliferation and differentiation. However, these compounds also have potent immunological properties, and may act by inhibition of cytokine production by keratinocytes or lymphocytes. Topical application of vitamin D analogues appears generally to be remarkably safe, but hypercalcaemia and hypercalciuria may develop if large quantities are used.


Quantification of n-alkanes in stratum corneum in the hereditary ichthyoses.

Chromatographic assay of n-alkanes in skin showed detectable levels in normal controls and in patients with various forms of hereditary ichthyosis. Raised n-alkanes were found in some, but not all, patients with non-bullous and bullous ichthyosiform erythroderma and in individual patients with lamellar ichthyosis, ichthyosis vulgaris and Netherton's syndrome. The finding of elevated scale n-alkanes is neither consistent in ichthyosis, nor specific to any one type of ichthyosis, and n-alkane assay is not helpful in distinguishing one type of hereditary ichthyosis from another. The source of n-alkanes in ichthyotic scale and their role, if any, in the pathogenesis of ichthyosis remain obscure.


Measurement of phosphoinositide-specific phospholipase C activity in mononuclear leucocytes from atopic and normal subjects.

The intracellular inositol pathway is an important route for cell activation and relies on the stimulation of membrane-bound phosphoinositide-specific phospholipase C (PLC). Previously we have shown abnormalities of inositol metabolism in mononuclear cells (MNL) in atopic dermatitis (AD) using an indirect method. We now describe a direct method of measuring PLC activity in membrane and cytosol preparations of MNL in AD. We compare PLC activity in AD with that in normal controls and examine the effect of substrate concentration and nucleotide stimulation on the system. Our findings show increased membrane-bound PLC activity in AD compared with normal controls. Non-specific stimulation of AD PLC activity by nucleotides suggests that the enzyme of atopics is more sensitive to substrate-driven activity than that of non-atopics.


Family history, smoking habits, alcohol consumption and risk of psoriasis.

We have conducted a multicentre case-control study to assess the epidemiological importance of previously suggested risk factors for psoriasis, including family history of the disease, smoking and alcohol consumption. Newly diagnosed psoriatics, with a history of skin manifestations no longer than 2 years were eligible as cases; as controls we selected subjects with newly diagnosed dermatological conditions other than psoriasis. Interviews were performed by trained medical investigators using a structured questionnaire. Two-hundred and fifteen cases, aged 16-65 years (median age 38), and 267 controls, aged 15-65 years (median age 36), were interviewed and included in the analysis. Family history was a risk factor for psoriasis; the multiple logistic regression (MLR) adjusted-odds ratio was 18.8 (95% confidence interval 6.4-54.8) for a history in parents, and 3.2 (95% confidence interval 1.5-6.6) for a history in siblings. The risk of psoriasis was higher for current smokers than for those who had never smoked. The MLR adjusted odds ratio was 2.1 (95% confidence interval 1.1-4.0) for people smoking 15 cigarettes or more per day. The risk of psoriasis was higher for alcohol drinkers: compared with teetotallers the MLR adjusted-odds ratios were 1.3 (95% confidence interval 0.8-2.3) for subjects drinking one or two drinks/day and 1.6 (95% confidence interval 0.9 to 3.0) for those drinking three or more. However, the trend in risk was not statistically significant. Our study confirms the role of family history in psoriasis and provides some evidence of a dose-response relationship for an association between smoking habits and psoriasis.


No evidence for a spirochaetal origin of localized scleroderma.

We looked for evidence of a Borrelia infection in 15 patients with morphoea. We were not able to detect antibodies to Borrelia burgdorferi in any of these 15 patients. None of the 14 skin biopsies examined by immunohistochemistry showed evidence of spirochaetes. Skin biopsies were cultured in 10 patients. All were negative. These results do not support a spirochaetal origin of localized scleroderma.


Disturbed extruding mechanism of lamellar bodies in dry non-eczematous skin of atopics.

A characteristic feature of non-eczematous atopic dry skin (DS) appears to be an impaired water permeability barrier (WPB) function. The WPB is constituted by intercellular lipid lamellae, located between the horny cells of the stratum corneum (SC), which are provided by exocytosis of lamellar bodies (LB). The aim of this study was to elucidate whether alterations in the dynamics of LB-extrusion could be responsible for this WPB disturbance. In an ultrastructural morphometric comparison the relative volume of LB in the two uppermost subcorneal layers in DS of atopics (n = 9) and healthy skin of controls (n = 7) was determined. The LBs were differentiated into extracytoplasmic LB, i.e. with the cell membrane already fused, and intracytoplasmic LB, i.e. entirely located within the cell. The total volume in the two cell layers of the stratum granulosum did not differ between atopics and controls. However, separate evaluation of the two LB-compartments revealed statistically significant differences between atopics and healthy controls. In the second uppermost cell layer of the stratum granulosum only 13% of the total LB volume of this layer had already fused with the cell membrane in the atopics as opposed to 42% in the controls. On the other hand more LB remained undelivered within the cells of the uppermost SG cell layer of the atopics (26% in atopics versus 8% in controls, P < 0.01). These findings suggest that a pathological extruding mechanism of LB in DS may be at least partly responsible for the recently detected biochemical alterations of epidermal lipids, and for the deficient WPB.


Selective activation of circulating CD4+ lymphocytes in severe adult atopic dermatitis.

An analysis of peripheral blood lymphocyte subsets and their expression of activation markers was performed using flow cytometry in 12 adult patients with severe atopic dermatitis, and compared with 14 normal individuals. Repeated measurements were made over an 8-week period during which disease activity was also assessed. Increased percentages of activated and unactivated CD4+ lymphocytes, and decreased percentages of CD8+ cells were observed in atopic dermatitis. Increasing disease activity was associated with an increase in the proportion of activated and unactivated CD4+ lymphocytes and a fall in the proportion of CD8+ cells. This study demonstrates that in adults with severe atopic dermatitis, increasing disease activity is associated with selective activation of CD4+ lymphocytes and a relative expansion of the CD4+ cell subset.


Possible mechanisms of immune modulation in chronic dermatophytoses: an in vitro study.

It has been suggested that patients with chronic superficial Trichophyton rubrum infection have defective cellular immunity to dermatophyte antigens. This may be due to a selective anergy to dermatophyte antigens or reflect the activity of dermatophyte-derived lymphocyte inhibitory factors. To explore these possibilities, we assessed lymphocyte transformation to a variety of recall antigens, including a cytoplasmic and exoantigen preparation of Trichophyton rubrum in 15 patients with chronic dermatophyte infection and 15 age- and sex-matched positive controls. In a duplicate set of experiments, autologous serum was replaced by heat-inactivated fetal calf serum. In addition, the direct effect of Trichophyton rubrum extracts on lymphoproliferation was assessed in vitro. Comparable lymphocyte transformation to each recall antigen was observed in patients and controls. Moreover, we found no evidence for a circulating dermatophyte-derived lymphocyte inhibitory factor in sera from patients with chronic superficial infection. A direct inhibitory effect of Trichophyton rubrum on lymphocyte proliferation to recall antigens was observed, however, at protein concentrations of > 10 micrograms/ml (exoantigen preparation) and > 25 micrograms/ml (cytoplasmic preparation). This inhibitory effect was rapidly reversible, not associated with loss of cell viability and maximal when added within 24 h of antigen to cultured lymphocytes. Class II MHC antigen HLA-DR, a surface marker of T-cell activation, was observed on inhibited lymphocytes co-cultured with antigen, suggesting the primary target for the inhibitory effect in vitro is the lymphocyte rather than the antigen-presenting cell.(ABSTRACT TRUNCATED AT 250 WORDS)


Characterization of inflammatory infiltrates in male pattern alopecia: implications for pathogenesis.

Hair-bearing, transitional, and alopecic scalp from three males and one female with progressive pattern alopecia were examined. Ultrastructural studies disclosed measurable thickening of the follicular adventitial sheaths of transitional and alopecic zones compared with those in the non-alopecic zones. This finding was associated with mast cell degranulation and fibroblast activation within the fibrous sheaths. Immunohistochemically, control biopsies were devoid of follicular inflammation (n = 3), while transitional regions consistently showed the presence of activated T-cell infiltrates about the lower portions of follicular infundibula. These infiltrates were associated with the induction of class II antigens on the endothelial linings of venules within follicular adventitia and with apparent hyperplasia of follicular dendritic cells displaying the CD1 epitope. Inflammatory cells infiltrated the region of the follicular bulge, the putative source of stem cells in cycling follicles. The data suggest that progressive fibrosis of the perifollicular sheath occurs in lesions of pattern alopecia, and may begin with T-cell infiltration of follicular stem cell epithelium. Injury to follicular stem cell epithelium and/or thickening of adventitial sheaths may impair normal pilar cycling and result in hair loss.


Topical vitamin C protects porcine skin from ultraviolet radiation-induced damage.

Ultraviolet radiation damage to the skin is due, in part, to the generation of reactive oxygen species. Vitamin C (L-ascorbic acid) functions as a biological co-factor and antioxidant due to its reducing properties. Topical application of vitamin C has been shown to elevate significantly cutaneous levels of this vitamin in pigs, and this correlates with protection of the skin from UVB damage as measured by erythema and sunburn cell formation. This protection is biological and due to the reducing properties of the molecule. Further, we provide evidence that the vitamin C levels of the skin can be severely depleted after UV irradiation, which would lower this organ's innate protective mechanism as well as leaving it at risk of impaired healing after photoinduced damage. In addition, vitamin C protects porcine skin from UVA-mediated phototoxic reactions (PUVA) and therefore shows promise as a broad-spectrum photoprotectant.


Increased levels of inflammatory cytokines in human skin lymph derived from sodium lauryl sulphate-induced contact dermatitis.

A superficial peripheral lymph vessel draining the skin of the upper and medial part of the foot was cannulated on the lower leg of six healthy human volunteers. After 2 days an irritant contact dermatitis was induced by application of 10% sodium lauryl sulphate to the area of skin drained by the lymph vessel. Three days later the spontaneously regressing skin reaction was treated with clobetasol propionate. Lymph was collected twice daily for 7 days, and the levels of various cytokines (IL-1 alpha, IL-1 beta, IL-2 and soluble IL-2 receptors, IL-6, IL-8, TNF-alpha, GM-CSF) were determined by ELISA technique. In the majority of the volunteers all cytokines examined were detected in several lymph samples, with the exception of IL-1 alpha and IL-8. In parallel with the clinical symptoms of the contact dermatitis the levels of IL-6 and TNF-alpha increased 8-10-fold, whereas for IL-1 beta, IL-2, IL-2 receptors, and GM-CSF there was a delayed, 2-3-fold increase. These results suggest that cytokines, in particular IL-6 and TNF-alpha, may actively participate in the immunological reactions in the skin and in the regional lymph nodes during contact dermatitis.