Natural interferon-alpha versus its combination with 6-methyl- prednisolone in the therapy of type II mixed cryoglobulinemia: a long- term, randomized, controlled study

Type II mixed cryoglobulinemia (MC) is an often progressive vasculitis characterized by circulating cold-precipitable proteins that usually consists of polyclonal IgG and monoclonal IgM kappa with rheumatoid factor (RF) activity. Its etiology is unknown, although recent evidence strongly suggests that hepatitis C virus (HCV) plays a major role. Plasmapheresis, corticosteroids, and cytotoxic drugs have been used in the therapy of MC patients. Recently, favorable results with recombinant interferon-alpha (rIFN alpha) have been reported. To further assess its effectiveness, we studied the effects of natural human interferon-alpha (nIFN alpha), alone and in combination with 6- methyl-prednisolone (PDN), in a prospective, randomized, controlled trial in patients with symptomatic MC. Sixty-five patients were enrolled onto the trial, 52 (80%) of whom presented serum anti-HCV antibodies and specific genomic RNA sequences. Fifteen patients received nIFN alpha (3 MU) intramuscularly (IM) three times weekly, whereas 17 patients also received 16 mg/d of PDN orally on non-IFN days. Moreover, 18 patients received 16 mg/d of PDN only, and 15 were untreated. Treatment was discontinued after 1 year and patients were monitored for 8 to 17 months (mean, 13). A complete response was achieved in eight of 15 patients (53.3%) treated with nIFN alpha and nine of 17 (52.9%) treated with nIFN alpha plus PDN, as compared with three of 18 patients (16.7%) who received PDN only (P < .05) and one of 15 (6.7%) untreated controls (P < .01). Partial response occurred in two of 15 (13.3%) patients treated with nIFN alpha, three of 17 (17.6%) who received nIFN alpha plus PDN, one of 18 (5.5%) who received PDN only, and one of 15 (6.7%) controls. A complete response in six patients (66.7%) was achieved within 3 months in the group that received nIFN alpha plus PDN, as compared with two patients (25%) of those who received nIFN alpha alone (P < .02). In anti-HCV-positive patients, the clinical response occurred in step with reduced or undetectable levels of HCV RNA and transaminase normalization. Quantification of circulating HCV RNA represented a good predictive response marker. The probability of relapse within 3 months after treatment was 100% (three of three patients) and 75% (six of eight patients), respectively, in patients who received PDN alone or nIFN alpha alone as compared with none of those who received nIFN alpha plus PDN (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Thyrotrophin-releasing hormone in human ejaculate

Immunoassayable TRH in human ejaculate was eluted from a gel column in a form with a molecular weight larger than that of the native peptide. With reverse-phase high-performance liquid chromatography (HPLC) the same activity co-eluted with standard TRH. Incubation of ejaculates at room temperature for 8 h was associated with a time-related increase in the total immunoassayable TRH. Analysis by HPLC of ejaculates after 12 h of incubation at room temperature indicated that, whereas the levels of the peptide co-eluting with native TRH declined with time, there was a concomitant increase in the concentration of a molecular species which also cross-reacted with the TRH antiserum, but which was more hydrophobic. The latter species is presumably identical to the tetrapeptide recently described by others and which may arise from the proteolytic degradation of secretory macromolecules. Although immunological activity was present in all six fractions of split ejaculates, the bulk of the peptide was associated with the later portions, implying a major vesicular contribution. However, secretions isolated from surgical preparations of the seminal vesicles contained undetectable levels of peptide, suggesting that the ejaculation process may represent a stimulus for its appearance in the semen. This study is further support for a local involvement of TRH in male reproductive function.     

Prolactin selectively stimulates ornithine decarboxylase in the lateral lobe of the rat prostate

In androgenized-hypophysectomized rats, ovine prolactin stimulated the activity of the ornithine decarboxylase (ODC) of the lateral lobes, but not the ventral and dorsal lobes of the prostate glands in a time- and dose-dependent fashion. High degrees of enzyme stimulation were associated with significant elevations in the endogenous levels of its product, putrescine. The relative response to prolactin over basal activities was relatively unaffected by indomethacin but decreased with cycloheximide, suggesting that prostaglandins do not mediate the effects of the hormone, but that a high rate of protein synthesis is a prerequisite for its expression. Indomethacin alone significantly increased the basal activity of the enzyme above control levels, suggesting that prostaglandins may normally exert a degree of inhibition on the ODC. The selective activation of the lateral lobe ODC supports previous reports of a differential response of the various prostatic lobes to prolactin, and also provides a convenient biochemical response for examining details of prolactin action on this organ.     

Microaggregate counts in frozen-preserved erythrocytes: effects of washing in three blood processors and filtration

Since microaggregates have been implicated in posttransfusion pulmonary insufficiency, their elimination has become an active concern in blood transfusion. Various types of filters, as well as frozen-preserved erythrocytes, have been used to provide blood relatively low in microaggregates. We have counted particles in frozen-stored blood before deglycerolization, after washing in each of three cell processing systems, and after filtration through a 40-micrometer filter. Washing frozen erythrocytes reduced the total particle counts by an average of 89%. Slight differences were found among the three blood processors with respect to particle removal. Passing washed blood through a 40-micrometer filter did not result in significant further reduction in particle counts. Hence, the use of such filters in a frozen-preserved blood system is not warranted.     

Use of healthcare a long time after severe burn injury; relation to perceived health and personality characteristics

Purpose.?The aim of the study was to evaluate which factors are associated with the use of healthcare a long time after severe burn injury.

Method.?After a review process based on clinical reasoning, 69 former burn patients out of a consecutive group treated at the Uppsala Burn Unit from 1980?–?1995 were visited in their homes and their use of care and support was assessed in a semi-structured interview. Post-burn health was assessed with the Burn-Specific Health Scale-Brief (BSHS-B) and personality was assessed with the Swedish universities Scales of Personality (SSP).

Results.?The participants were injured on average eight years previously. Thirty-four had current contact with healthcare due to their burn injury and had significantly lower scores on three BSHS-B-domains: Simple Abilities, Work and Hand function, and significantly higher scores for the SSP-domain Neuroticism and the SSP-scales Stress Susceptibility, Lack of Assertiveness, and lower scores for Social Desirability. There was no relation to age, gender, time since injury, length of stay, or to the surface area burned.

Conclusions.?A routine screening of personality traits as a supplement to long-term follow-ups may help in identifying the patient's need for care.     

Androgen Binding Proteins and Androgen Levels in the Human Testis and Epididymis

The human testis and epididymis contain two distinct androgen binding components, one with physicochemical properties identical to the androgen receptor found in other target tissues and another, androgen binding protein (ABP), which shares the same binding characteristics as human testosterone binding globulin (TeBG). Simultaneous assays of ABP and corticosteroid binding globulin (CBG, an exclusive blood protein) in the same testicular extracts suggest that androgen binding to the second component could be readily explained by contamination with blood TeBG rather than by the existence of a testis specific ABP. The levels of dihydrotestosterone (DHT) (the major androgen binding to this protein) in the human epididymis are much lower than those reported for rats and rabbits. Furthermore, there is no concentration gradient in DHT or testosterone along the human epididymis.