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The HIV protease substitution L76V, in combination with M46I, confers clinically relevant levels of lopinavir resistance and represents a novel resistance pathway to first-line lopinavir/r therapy.

1. Prolactin is a 21,500 Dalton single-chain polypeptide hormone but may occur in 50 kDa and 150 kDa molecular variants. 2. These large PRL variants may be secreted predominantly; this condition is termed "macroprolactinemia". It is characterized by high immunological and normal biological serum levels of prolactin, and lack of clinical symptoms of hyperprolactinemia. 3. The information on PRL is encoded on chromosome 6. Transcription can be enhanced and suppressed by a variety of hormonal factors. 4. PRL is secreted in a pulsatile fashion; it displays a circadian rhythm (with a maximum during sleep) and is stimulated by some amino acids. PRL also responds to mechanical stimulation of the breast. 5. PRL rises during pregnancy, and maintainance of hyperprolactinemia (and, thereby, physiological infertility) is dependent on the frequency and duration of breast feedings. 6. Hypothalamic regulation of prolactin mainly involves tonic inhibition via portal dopamine. The physiological importance of various stimulating factors present in the hypothalamus is still incompletely understood. In particular, there is still no place for TRH in PRL physiology. 7. PRL is released in response to stress; this response may be mediated by opioids. The low-estrogen, low-gonadotropin amenorrhea of endurance-training women is not mediated by prolactin, however. 8. Estrogens stimulate PRL gene transcription via at least two independent mechanisms. There are many clinical examples of this estrogen effect on prolactin serum levels, and also on the growth of prolactinomas. 9. Mild hyperprolactinemia remains an enigma which cannot satisfactorily be resolved by biochemical or radiological testing. The border between "normal" and "elevated" prolactin is ill-defined. The possibility of macroprolactinemia complicates this matter even further. 10. The number of drugs which suppress prolactin by acting on pituitary D2 receptors, and which are useful in the treatment of hyperprolactinemia, continues to increase. In the field of ergot alkaloids, parenteral application appears to be a logical solution to the problem of the high first-pass effect; in addition, this form of treatment is frequently better tolerated than the oral route. 11. Prolactinoma development is presently being studied employing molecular biological techniques; the question of whether tumorigenesis can be attributed to specific defects of gene regulation remains to be answered.

The optimal duration of treatment for catheter-related Staphylococcus aureus bacteremia is not known. Short courses (< or = 2 weeks) of therapy should be viewed with caution because essential data on late complications, such as osteomyelitis and metastatic abscesses, are lacking. This study represents a retrospective analysis of the data from 49 adult patients hospitalised in the period 1994-1996 (mean age, 57 years; range, 20-90 years; 47% male) and from whom Staphylococcus aureus was cultured concomitantly from peripheral blood and catheter segments. Forty-six venous catheters, two arterial catheters, and one unknown type of catheter were used. Forty-four patients were treated with effective anti-Staphylococcus aureus antibiotics. Twenty patients had a favourable outcome, defined as no complication and no death during 1 year of follow-up, 24 patients had complications, 14 patients died due to attributable mortality, and 5 other patients died of an underlying disease without showing signs or symptoms of a complication. Patients were categorised according to the duration of treatment. There were small differences between a shorter (1-14 days) and a longer (>14 days) course of antibiotics with regard to favourable outcome (41% vs. 33%), complications (48% vs. 53%), attributable death (31% vs. 20%), and death due to underlying disease (41% vs. 33%), respectively. The rates of complications and death were high, but a definite conclusion cannot be drawn because the study was underpowered. More randomised trials are needed, but, until the results of such trials are available, the duration of therapy should not be shortened to less than 14 days.

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