Spinal Cord Stimulation for Severely Ischemic Limbs

Severe atherosclerosis of the lower limbs causes rest pain, skin ulcerations and gangrene. In such situations and when standard surgical treatment had failed or it is impossible to employ, spinal cord stimulation (SCS) seems to be of value. Since April 1985, we have used this technique on 19 patients. The results have been beneficial in 70.6% of the cases and have shown some evidence of increasing cutaneous flow. However, randomized series are required before accepting it as having a special place in the fight against atherosclerotic disease.     

Pyridoxine-Responsive Anemia: Report of 2 Cases in Brothers and a Review of the Literature

The clinical and laboratory findings in two brothers with severe anemiaare presented. These findings were very similar in both cases. Evidence thatat least one of them suffered from a pyridoxine-responsive anemia is presented.It was assumed that the other had the same disorder since, in addition to thestriking similarity in the clinical and laboratory abnormalities, the latter’s anemia disappeared completely with the parenteral administration of vitamin Bcomplex, which provided him with 2 mg. of pyridoxine daily. These patientshave not relapsed 1.5 and 6 years after stopping the therapy.

A review of the reported cases with anemia responding to vitamin B₆ administration is presented. Common factors observed in some of these casesare: (1) severe anemia, microcytic and hypochromic in type, chiefly due to astriking maturation erythroblastic arrest at the basophilic stage with no defectin leukocytes or thrombocytes; (2) hyperferremia and hemosiderosis; (3) anabnormal tryptophan-loading test; and (4) complete or almost complete correction of all abnormalities with administration of vitamin B₆, even at smalldoses. These data were considered to suggest that the patients had a true deficiency in pyridoxine.

In other patients, no increased excretion of xanthurenic acid has been observed after a tryptophan-loading dose, and pyridoxine administration hasimproved the anemia only partially and has not reversed the serum iron parameters to normality. All of these other patients suffered from a familial hypochromic anemia not due to iron deficiency or from a "sidero-achrestic" or "refractory normoblastic" anemia.

The cause of the disorder in patients in the first group is unknown, but, byexclusion, increased requirement of vitamin B₆ seems to be the most likelypossibility.

Submitted on November 22, 1960 Accepted on February 14, 1961     

Computer analysis of corneal innervation density using a novel double stain in rat corneal whole mounts

Computerised morphometry and a double stain technique were utilised to examine the corneal nerves in whole mounts. This novel stain combines the nonspecific acetylcholinesterase(NsAchE) and gold chloride(AuCl) procedures to enhance staining contrast and facilitate computerised detection of corneal nerves. Fresh rat corneas were dissected, and the Descemet's membrane-endothelium complex was removed. Then the corneas were fixed in 4% paraformaldehyde with 50 m m Na-K phosphate buffer (pH 7.2) and 8% sucrose for 30 min. They were rinsed and stained singly with NsAchE or AuCl, or were double stained using NsAchE followed by AuCl. Between NsAchE and AuCl staining the corneas were stored frozen in OCT compound at −70°C. Flat mounts of whole corneas were photographed before and after the second staining. Measurable stromal innervation density (mean± S.D. ) in age-matched corneas stained with AuCl(3.90±0.36 mm/mm²) was not significantly different from that of NsAchE stained corneas. However, double staining compared with NsAchE staining of the same corneas revealed a 48±27% increase in demonstrable innervation density of the subepithelial nerve plexus (7.95±0.86 mm/mm² vs 5.52±1.31 mm/mm², respectively). Improved visualisation of epithelial nerves and their fine ramifications (leashes) was also obtained by double staining. This novel combination of 2 procedures enhances the detection of corneal nerves for analysis by computerised morphometry and provides a more representative estimate of total corneal innervation density.     

Pharmacokinetic Sub-Study in the SPIRIT III Randomized and Controlled Trial of XIENCE V® Everolimus Eluting Coronary Stent System

Background: Drug-eluting stents (DES) are widely used for treatment of coronary artery disease with benefit of reduced restenosis compared to bare metal stents. The XIENCE V ^® Everolimus Eluting Coronary Stent System is a second-generation DES system for better deliverability while maintaining safety and efficacy profiles. The present pharmacokinetic sub-study from the SPIRIT III Randomized and Controlled Trial (RCT) was to evaluate systemic exposure of patients to everolimus and to further demonstrate safety following implantation of XIENCE V ^® stents with everolimus doses ranging from 53 to 181 μg.
Methods and Results: Drug concentrations in whole blood were determined at multiple time points using a validated analytical method with a limit of quantification of 0.1 ng/mL. Individual C_max ranged from 0.17 to 2.40 ng/mL and occurred between 0.07 and 1.88 hours across all dose levels. Both mean and individual C_max values were below the trough blood concentrations of everolimus (Certican^®) for inhibition of organ transplant rejection. The last time point at which drug concentrations could be quantified ranged from 12 to 168 hours postimplantation in individual patients. In most cases, the blood levels dropped below the limit of quantification after 72 hours.
Conclusions: This study confirms that the XIENCE V ^® stent causes a limited and systemic exposure to everolimus. The presumed localized and efficient delivery of everolimus to target vessels coupled with limited and transient systemic drug exposure contributes to the safety and effectiveness of the XIENCE V ^® EECSS in patients of SPIRIT III RCT for longer than 2 years. (J Interven Cardiol 2010;23:26–32)     

NEVUS SEBACEUS: CLINICAL OUTCOME AND CONSIDERATIONS FOR PROPHYLACTIC EXCISION

Background and Objective. Nevus sebaceus is a hamartoma of the skin with the potential to develop benign and malignant neoplasms. Prophylactic surgical excision has been advocated, usually before puberty, to prevent their occurrence; however, it is the clinical impression of the authors that the development of cutaneous neoplasms is infrequent and, if they develop, they are usually benign and nonaggressive. Our objective was to investigate the clinical outcome and histopathologic findings of every single nevus sebaceus that had been excised in our institution in a five-year period. Methods. Two hundred and twenty-five consecutive cases, coded as nevus sebaceus corresponding to 175 patients were submitted to our institution between September 1987 and May 1992, and were identified among a total of 64,827 specimens. All cases were reviewed histopathologically and clinical information was obtained from the records. Specimens from 10 patients were excluded. Results. A total of nine benign neoplasms (5.4%) were identified in the 165 patients. Three patients were in their second decade of life, two in their third, two in the fifth and two in the sixth. There were five trichoblastomas, three specimens of syringocystadenoma papilliferum, and one aprocrine cystadenoma. No malignant neoplasms were found. Six of the tumors were removed either for prophylactic or cosmetic reasons and in only three cases were the neoplasms suspected clinically and excised. Conclusions. If this same tendency prevails in other prospective studies, we strongly believe that prophylactic excision of all nevus sebaceus is not warranted. Excision should be recommended only when benign or malignant neoplasms are clinically suspected or for cosmetic considerations.     

PUVA therapy prevents sensitization to mechlorethamine in patients with psoriasis

Two groups of 20 patients with psoriasis were treated with mechlorethamine applied topically (group A) or with PUVA combined with mechlorethamine (group B). In group B mechlorethamine was started after six PUVA treatments. Results showed a significant decrease of the incidence of contact dermatitis in group B (30%) compared with group A (75%). Allergic dermatitis, demonstrated by a positive patch test to mechlorethamine with an histology of eczema, was observed in 55% of patients in group A and 20% in group B. The incidence of irritant dermatitis was not significantly different in the two groups. Allergic dermatitis was observed later in group B: after an average of 32.2 applications of mechlorethamine compared with 25 applications in group A. Possible mechanisms responsible for these results are reduction of epidermal Langerhans cells by PUVA therapy and induction of antigen-specific suppressor T cells. Patients living far from a specialized centre might be treated initially with PUVA therapy then with mechlorethamine alone, at home. This schedule may reduce the incidence of contact dermatitis to mechlorethamine.