GABA(A) receptor active steroids are altered in epilepsy patients with tuberous sclerosis.

BACKGROUND: The neuroactive steroid 3alpha, 5alpha-tetrahydroprogesterone is the most potent endogenous positive modulator of gamma-amino-butyric acid (GABA)(A) receptors. There is evidence for a relation between neuroactive steroids and seizure susceptibility. OBJECTIVE: To evaluate the putative role of counteregulator neuroactive steroids in the occurrence of seizures in patients with tuberous sclerosis. METHODS: Plasma concentrations of the enantiomers 3alpha, 5alpha- and 3alpha, 5beta-tetrahydroprogesterone (3alpha(s)-THP), which are positive modulators of GABA(A) receptors, were measured in 18 patients, along with their endogenous functional antagonists 3beta, 5alpha- and 3beta, 5beta-THP (3beta(s)-THP), to assess their possible modification compared with control subjects. Neuroactive steroids were assayed using a highly sensitive and specific gas chromatographic/mass spectrometric method. RESULTS: In the tuberous sclerosis patients with poorly controlled seizures, there was a significantly lower 3alpha(s)/3beta(s)-THP ratio than in seizure-free patients or control subjects. CONCLUSIONS: The reduced 3alpha(s)/3beta(s)-THP ratio may decrease GABAergic tone, contributing to the appearance of seizures in tuberous sclerosis patients with epilepsy.

Analysis of 11-nor-9-carboxy-delta(9)-tetrahydrocannabinol in biological samples by gas chromatography tandem mass spectrometry (GC/MS-MS).

Gas chromatography tandem mass spectrometry (GC/MS-MS) analysis of 11-nor-carboxy-delta(9)-tetrahydrocannabinol (delta(9)-THC-COOH), the major metabolite of delta(9)-tetrahydrocannabinol, in biological samples is reported. The proposed method, using deuterated delta(9)-THC-COOH as an internal standard, is able to detect the major metabolite of cannabis derivatives at very low levels (picograms/millilitre) with high specificity. These characteristics render the proposed analytical procedure suitable for confirmatory analysis in drug testing for cannabis use.

Double recurrence of FSGS after two renal transplants with complete regression after plasmapheresis and ACE inhibitors.

A patient who had undergone a first cadaveric donor kidney transplantation for idiopathic focal segmental glomerular sclerosis (FSGS), had an immediate recurrence of a biopsy-proven FSGS that eventually led to graft failure within 5 years from transplantation. The patient underwent a second cadaveric transplantation 10 months later. An immediate recurrence of a biopsy-proven FSGS occurred that was treated with two protracted cycles of plasmapheresis of seven months each, with the addition of an ACE inhibitor from the beginning. A complete and stable remission of FSGS was observed, which continues after more than 6 years from the end of plasmapheresis. The recurrence of FSGS after a second transplantation has a poor prognosis, but prolonged plasmapheresis treatment, by removing circulating factors altering glomerular permselectivity, and the addition of ACE inhibitors, through their potential interference with TGF-beta, might be synergistic in obtaining permanent remission.

A case of hemolytic disease of the newborn due to anti-Kpa.

A patient with hemolytic disease of the newborn (HDN) due to maternal anti-Kpa alloimmunization is described. Although there are few reports in the literature, it appears that HDN due to anti-Kpa is often mild and transfusion therapy is rarely required. However, in this case, the baby's hemoglobin progressively decreased and on day 18 a blood transfusion was administered, but jaundice was not severe enough for exchange transfusion.

Transcutaneous ethanol injection in hepatocarcinoma: problems in analgesia and sedation.

Therapeutic ethanol injection into primitive or secondary hepatic tumours if performed in "one shot" causes a great deal of pain. For this reason an analgesic/sedation protocol was devised. This relies on the administration of ketorolac-propofol-nitrogen oxide mixture that has been used to treat patients with neoplastic hepatic diseases. A 20 patient series is described. Analgesic protocol was very effective and the only drawbacks were a residual sleepiness than in part is probably dependent on ethanol emigration into the bloodstream and consequently to the central nervous system depression.

Usefulness of plasma exchange in recurrent nephrotic syndrome following renal transplant.

Nephrotic syndrome due to focal segmental glomerulosclerosis (FSGS) frequently recurs even after transplantation and may cause failure of the renal allograft. We report a case in which plasma exchange (PE) was used to treat a 32-year-old patient with biopsy-proven recurrence of FSGS in a second renal transplant after the first allograft had failed. One year after the second renal graft, the patient presented with proteinuria of 5 g/day and a creatinine level of 1.46 mg/dl. A course of 9 PE was performed over a 15-day period. Proteinuria improved rapidly, and 20 days after the last PE, it was already down to 0.8 g/day. This level continued to decrease progressively (0.5 g/day after 3 months) and reached zero after approximately 6 months. Eleven months after PE treatment, the patient had no proteinuria and his plasma creatinine level was normal. In our opinion PE should be instituted early in recurrent nephrotic syndrome after renal transplantation. The optimum frequency of such treatment still has to be established, especially with regard to its use as long-term maintenance therapy.

Refractory thrombotic thrombocytopenic purpura: successful treatment by plasmapheresis with plasma cryosupernatant.

BACKGROUND: Plasma exchange (PE) with reinfusion of fresh frozen plasma (FFP) is the therapy of choice for thrombotic thrombocytopenic purpura (TTP) in the acute phase. About 20% of patients do not respond fully to this treatment and can suffer relapse. The plasma cryosupernatant (PCS) fraction depleted of the largest von Willebrand factor (vWF) multimers, considered to be among the possible causes of relapse, has recently been suggested as an alternative to FFP. METHODS: We submitted three patients in TTP relapse to plasma exchange with reinfusion of PCS. This treatment was associated with anti-platelet agents in two of the patients. RESULTS: Infusion of PCS led to a rapid improvement of the clinical picture in all three patients, with a return to normal of the reference parameters (platelet count' serum LDH). A few days after suspending PE, the patient not receiving anti-platelet treatment suffered another relapse which was definitively resolved with resumption of PE and administration of anti-platelet agents. CONCLUSIONS: We consider PCS to be a valid alternative treatment for TTP relapses, and we have found that the best results are obtained when it is associated with anti-platelet agents.

Ascorbic acid specific utilization by some yeasts.

One hundred and eighty strains of yeasts belonging to 17 genus and 53 species were screened for their ability to grow on ascorbic acid and iso-ascorbic acid as the sole carbon source. Most of the tested strains (157) were unable to grow on either compound. Strains of seven species of the genus Cryptococcus, of two Candida species, of Filobasidiella neoformans, Trichosporon cutaneum, Lipomyces starkeyi, Hansenula capsulata, and one strain of Aureobasidium pullulans were able to grow on ascorbic as well as on iso-ascorbic acid. Conversely, four strains of Aureobasidium pullulans, Candida blankii, and Cryptococcus dimennae could use only ascorbic acid for growth.

Production of amylase(s) by Schwanniomyces castellii and Endomycopsis fibuligera.

Schwanniomyces castellii and Endomycopsis fibuligera Produced extracellular amylase(s) when grown on various carbon sources and at different pH values. Both yeast species showed significant amylase synthesis in the presence of either maltose or soluble starch. On the other substrates tested (glucose, cellobiose, sucrose, trehalose, melezitose, raffinose, ethanol, glycerol) differences were found regarding growth and amylase production. Free glucose in the culture medium apparently inhibited enzyme synthesis. The pH range allowing maximal growth and amylase production was 4.5-6.0 for E. fibuligera and 5.5-7.0 for S. castellii.