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Query: UMLS:C0020538 (hypertension)
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The tumescent technique for local anesthesia permits regional local anesthesia of the skin and subcutaneous tissues by direct infiltration. The tumescent technique uses large volumes of a dilute anesthetic solution to produce swelling and firmness of targeted areas. This investigation examines the absorption pharmacokinetics of dilute solutions of lidocaine (0.1% or 0.05%) and epinephrine (1:1,000,000) in physiologic saline following infiltration into subcutaneous fat of liposuction surgery patients. Plasma lidocaine concentrations were measured repeatedly over more than 24 hours following the infiltration. Peak plasma lidocaine levels occurred 12-14 hours after beginning the infiltration. Clinical local anesthesia is apparent for up to 18 hours, obviating the need for postoperative analgesia. Dilution of lidocaine diminishes and delays the peak plasma lidocaine concentrations, thereby reducing potential toxicity. Liposuction reduces the total amount of lidocaine absorbed systemically, but does not dramatically reduce peak plasma lidocaine levels. A safe upper limit for lidocaine dosage using the tumescent technique is estimated to be 35 mg/kg. Infiltrating a large volume of dilute epinephrine assures diffusion throughout the entire targeted area while avoiding tachycardia and hypertension. The associated vasoconstriction is so complete that there is virtually no blood loss with liposuction. The tumescent technique can be used with general anesthesia or IV sedation. However, with appropriate instrumentation and surgical method, the tumescent technique permits liposuction of large volumes of fat totally by local anesthesia, without IV sedation or narcotic analgesia.
J Dermatol Surg Oncol 1990 Mar
PMID:Tumescent technique for regional anesthesia permits lidocaine doses of 35 mg/kg for liposuction. 217 48

At therapeutic drug levels, the functional changes which occur are a reduction of glomerular filtration rate and renal plasma flow. At higher doses, morphological changes develop which may result, particularly in severe cases, in acute or chronic renal failure. The threshold for the development of irreversible vascular-interstitial lesions mainly depends on the increment of serum creatinine, age and drug dosage or drug blood level. Based on the experience with cyclosporin A (CyA), the following recommendations have been made for its clinical use, especially in patients with autoimmune diseases. The initial dose should not exceed 5 mg/kg body weight and the dose should be reduced if blood CyA levels are over 250 ng/ml; in addition, a dose reduction is recommended if serum creatinine values exceed 30% of pre-treatment values or if other signs of CyA toxicity, such as hepatotoxicity or hypertension, are found. Strict adherence to these suggestions should allow treatment of patients for prolonged periods without irreversible morphological lesions.
Br J Dermatol 1990 Jun
PMID:Renal side-effects of cyclosporin A with special reference to autoimmune diseases. 219 77

This is a review of the clinical studies performed so far in The Netherlands of the treatment of psoriasis with cyclosporin A (CyA), a selective immunosuppressive drug that has caused a major breakthrough in transplant medicine. Data derived from a double-blind placebo-controlled study (5 mg/kg/day of CyA), dose-finding studies (2.5 mg vs 5 mg/kg/day and 1 mg, 2 mg or 3 mg/kg/day), and long-term treatment of chronic plaque-type psoriasis (1.1-7.2 mg/kg/day) suggest an initial starting dose of 3 mg/kg/day irrespective of the severity of the disease. Long-term treatment brought about dose- and time-dependent (reversible) side-effects, including renal dysfunction and hypertension. Efforts to reduce the dose included concomitant administration of drugs known to have anti-psoriatic efficacy. Only combination with topical steroids appeared to add to the clinical efficacy of CyA, but did not allow a dose reduction sufficient to restore renal function. Dose reduction through intermittent treatment, however, postponed exacerbations sufficiently to permit at least partial normalization of serum creatinine levels. A similar effect was seen in the treatment of pustular palmoplantar psoriasis, which responded to doses of 1.1-6.1 mg/kg/day.
Br J Dermatol 1990 Jun
PMID:Oral cyclosporin A in the treatment of psoriasis: an overview of studies performed in The Netherlands. 219 81

This is a review of the side-effects of cyclosporin A (CyA) in patients with severe psoriasis; renal dysfunction and hypertension are discussed elsewhere. In particular, paraesthesia, hypertrichosis, gingival hyperplasia and gastrointestinal disorders may occur, but are generally transient, mild-to-moderate in severity and only rarely require discontinuation of CyA. Infections are not a problem. As expected with an immunosuppressive drug, there is the possible risk of tumour development, particularly squamous cell carcinomas. However, these skin malignancies developed almost exclusively in patients previously treated with PUVA and/or methotrexate. The few lymphoproliferative disorders regressed spontaneously on discontinuation of the drug. Whether the isolated cases of solid tumours were CyA-related is not known. Apart from a raised serum creatinine, an important indicator of renal dysfunction, the laboratory abnormalities included hypomagnesaemia, hyperkalaemia, increased uric acid, changes in liver function tests, and fluctuations in the serum cholesterol and triglyceride levels. Although most of these changes were not clinically relevant, laboratory monitoring of patients with psoriasis treated with CyA is essential.
Br J Dermatol 1990 Jun
PMID:Side-effect profile of cyclosporin A in patients treated for psoriasis. 219 84

Serum creatinine and blood pressure were measured in patients who had severe psoriasis and who were treated with cyclosporin A (CyA) in initial doses of 1.25 mg (n = 34), 2.5 or 3 mg (n = 314), or 5 (n = 215) mg/kg/day. Of the 563 patients involved, 201 were treated for more than 3 months, and 100 received CyA continuously for 12 months or more. Sixty-eight additional patients were included as controls and received placebo (n = 42) or etretinate (n = 26). At doses of 2.5 and 5 mg/kg/day, CyA induced slight but significant dose-dependent increases in serum creatinine and blood pressure. Creatinine increases of 50% or more over baseline values were detected in 4% of the patients receiving 2.5 mg/kg/day and in 13% of those receiving 5 mg/kg/day. After an initial rise during the first weeks of treatment, mean creatinine level remained stable over 1 year provided that the CyA dose was reduced whenever creatinine levels increased by 30% or more over baseline. The incidence of hypertension was 10.6% and did not vary whether the CyA dose was 2.5 or 5 mg/kg/day. The first elevated blood pressures were recorded early after starting CyA therapy (median: 1 month). However, 3 months after stopping treatment, the increases in creatinine as well as in blood pressure were reversible and the levels did not significantly differ from baseline values.
Br J Dermatol 1990 Jun
PMID:Renal function and blood pressure in psoriatic patients treated with cyclosporin A. 219 85

The side-effects of long-term cyclosporin A (CyA) treatment in 26 patients with severe psoriasis were evaluated. These patients had a mean PASI score of 30.2 and were treated with CyA for between 7 and 37 months (mean 19.5 months). There were three groups according to the dose of CyA, less than 2 mg/kg per day, 2-3 mg/kg per day and greater than 3 mg/kg per day. In all three groups, CyA was found to be equally effective. Treatment with CyA was discontinued in 12 of the 26 patients because of nephrotoxicity and/or development of hypertension. One was in the less than 2 mg/kg per day group, three were in the 2-3 mg/kg per day group and eight in the greater than 3 mg/kg per day group. There was no hepatotoxicity with CyA treatment. One patient developed two squamous cell carcinomas of the skin.
Br J Dermatol 1990 Sep
PMID:Analysis of side-effects of medium- and low-dose cyclosporin maintenance therapy in psoriasis. 220 73

Scleroderma developed in six women who were taking L-tryptophan. Fasciitis and morphea were most common, but one patient had pleural effusion, hypertension, and signs of cardiac and kidney failure. In five patients the biopsy findings were characteristic of scleroderma; the sixth patient had Crohn's disease and developed fasciitis; her biopsy specimen showed inflammatory arteritis. All patients' conditions improved after cessation of their L-tryptophan intake, initiation of corticosteroid therapy, or both. These findings confirm previous data that show altered tryptophan-kynurenine metabolism in some patients with scleroderma and fasciitis, particularly with tryptophan loading.
J Am Acad Dermatol 1990 Sep
PMID:Scleroderma and L-tryptophan: a possible explanation of the eosinophilia-myalgia syndrome. 221 43

Since 1984, cyclosporine has been used increasingly for indications other than in prophylaxis of transplant rejection. Current awareness that psoriasis is, at least in part, a T cell-mediated condition has led to the initiation of several studies of cyclosporine's role in the treatment of this disease. The remarkable efficacy of systemically administered cyclosporine, even in severely refractory cases of psoriasis, has not only provided us with a new therapeutic option but also has helped further our understanding of the pathophysiology of psoriasis. Although it has been hailed as a breakthrough, systemic cyclosporine usage is associated with undesirable sequelae, principally hypertension and decreased renal function. These effects limit its more widespread use. This review assesses current knowledge of the capabilities and prospects of systemic cyclosporine in the treatment of psoriasis, as well as the status of topical preparations.
J Am Acad Dermatol 1990 Dec
PMID:Systemic and local administration of cyclosporine in the treatment of psoriasis. 227 31

Renal dysfunction is a frequent consequence of cyclosporine administration, even when cyclosporine blood concentrations are maintained within proper therapeutic levels. As dermatologic indications for this compound expand, it is important for clinicians to understand the relevant pharmacology and physiology that underlie cyclosporine-induced renal dysfunction. This article reviews the clinical pharmacology of cyclosporine, the principles of renal function testing, and the clinical manifestations of this drug's effects on the kidney. Sudden declines in kidney function, long-term cyclosporine nephrotoxicity, hemolytic-uremic syndrome, and hypertension are discussed from a clinical and experimental standpoint. Finally, practical suggestions are provided to aid the dermatologist in managing cyclosporine-treated patients.
J Am Acad Dermatol 1990 Dec
PMID:Renal effects of cyclosporine. 227 36

Forty-four patients with severe psoriasis have been treated with cyclosporin A (CyA) for 2-50 months (mean 17 months). During the study, 31 (70%) of these patients achieved a greater than 70% reduction in PASI score, 39 (88%) achieved a greater than 60% reduction and 42 (95%) a greater than 50% reduction. The mean initial dose of CyA was 3 mg/kg/day and the mean dose was 3.3 mg/kg/day throughout the study. Twenty-five (57%) patients were maintained on less than or equal to 3 mg and six (14%) required greater than 5 mg/kg/day for limited periods to obtain significant improvement. In three of these patients, this was achieved with 6 mg/kg/day but, of the remainder, one required 7 mg and two required 10 mg/kg/day. Of the 44 patients, 32 (73%) are still taking CyA. Patients were discontinued because of: side-effects directly attributable to treatment (n = 4); remission of psoriasis (n = 4); death (n = I); defaulting (n = I); infrequent attendance (n = I); high doses of NSAID were necessary for arthritis (n = I). Before starting CyA, 39 patients were normotensive; 21 (54%) developed mild hypertension. In 28 patients where the GFRs were estimated before and during treatment, there was a 16% reduction (P less than 0.0001) during a mean period of 8 months. Two patients developed malignancies. The incidence of hypertension and percentage decrease in GFR were strongly correlated with the dose required to control the psoriasis.
Br J Dermatol 1990 Jun
PMID:Four years of experience with cyclosporin A for psoriasis. 236 68


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