Safety of GM-CSF in patients with AIDS: a review of the literature

We performed a literature search for all clinical studies reporting outcomes in patients with the acquired immunodeficiency syndrome (AIDS) receiving granulocyte-macrophage colony-stimulating factor (GM-CSF) for any indication. Safety outcomes included human immunodeficiency virus replication, immune status, and frequency of opportunistic infections and neoplasms. Data were synthesized qualitatively. We identified 22 studies (274 patients): 12 addressed AIDS neutropenia, 8 AIDS cancer therapy, and 2 opportunistic infections. Viral burden was assessed by serum p24Ag in 15 studies. Nine reported no change in levels, three net decreases, and three net increases. All studies showing net increases involved patients receiving GM-CSF without a concurrent antiretroviral. The CD4 counts were unchanged in 5 studies, increased in 3, and not reported in 14. The incidence of neoplasms or new opportunistic infections was low. The literature suggests no increased risk of viral replication or clinical deterioration in patients with AIDS who take GM-CSF concurrently with zidovudine.     

Renin-1 is essential for normal renal juxtaglomerular cell granulation and macula densa morphology

The secretion of renin from granules stored in renal juxtaglomerular cells plays a key role in blood pressure homeostasis. The synthesis and release of renin and the extent of granulation is regulated by several mechanisms including signaling from the macula densa, neuronal input, and blood pressure. Through the use of a gene-targeting vector containing homology arms generated using the polymerase chain reaction, we have inactivated the Ren-1(d) gene, one of two mouse genes encoding renin, and report that lack of renin-1(d) results in altered morphology of the macula densa of the kidney distal tubule and complete absence of juxtaglomerular cell granulation. Furthermore, Ren-1(d-/-) mice exhibit sexually dimorphic hypotension. The altered growth morphology of the macula densa in Ren-1(d)-null mice should provide a tool for the investigation of the JG cell-macula densa signaling. Furthermore, the current data indicate that expression of the Ren-1(d) gene is a prerequisite for the formation of storage granules, even though the related protein renin-2 is present in these mice, suggesting that renin-1(d) and renin-2 are secreted by distinct pathways in vivo.     

hTom34: a novel translocase for the import of proteins into human mitochondria

Most mitochondrial proteins are nuclear encoded, synthesized on cytosolic ribosomes, and imported into the mitochondria. We have identified and characterized a 309 amino acid human protein with a molecular weight of 34 kDa that functions as a subunit of the translocase for the import of such proteins. hTom34 (34-kDa Translocase of the Outer Mitochondrial Membrane) is displayed on the surface of mitochondria and is resistant to extraction under alkaline conditions. Antibodies raised against hTom34 specifically inhibit in vitro import of the mitochondrial precursor protein preornithine transcarbamylase into mitochondria isolated from rat liver. Based on trypsin digestion experiments, the receptor has a large (27 kDa) C-terminal domain exposed to the cytosol. This novel component of the protein import machinery possesses a 62 residue motif conserved with the Tom70 family of mitochondrial receptors but otherwise appears to have no counterpart so far characterized in the mitochondria of any other species.     

Importance of a conserved phenylalanine-35 of cytochrome b5 to the protein's stability and redox potential [published erratum appears in Protein Eng 1997 Aug;10(8):983]

Phenylalanine-35, which is a residue of the hydrophobic patch on the surface of cytochrome b5, has been mutated into Tyr35, His35 and Leu35 to elucidate the functions of the Phe35 and give further insight into the roles of the hydrophobic patch and/or aromatic network. The effects of these mutations on the heme environment, denaturation towards heating and the denaturant urea, redox potential and stability of protein were studied. The relative stability of cytochrome b5 and its mutants towards heating has the order Phe35Tyr > wild type > Phe35Leu > Phe35His in the oxidized state and wild type > Phe35Tyr > Phe35Leu > Phe35His in the reduced state. All the mutants exhibit decreased reduction potentials: Phe35Tyr -66 mV, Phe35His -51 mV and Phe35Leu -28 mV, which are more negative than that of the wild type. The order of redox potential reflects the relative stability in the oxidized and reduced states. A method of producing multiple mutants at a single site of a gene is also described for the first time.      

Detection of glove puncture and skin contamination during caesarean section

Measures that can be taken to reduce exposure to potentially infected body fluids are of particular relevance in obstetric and gynaecological surgery due to high rates of glove puncture and relatively higher prevalence of human immunodeficiency virus seropositivity in the obstetric age group. We describe the use of a simple electronic device that alarms following puncture of surgical gloves or the creation of a fluid bridge between surgeon and patient. Further exposure to potentially infected body fluids is thus prevented. This present study was performed in the context of caesarean section, but the application of the technique to gynaecological procedures is appropriate.     

Chest radiography in the ICU

Proper positioning and assessment of abnormalities and complications of the above-mentioned devices have a significant impact on the management of critically ill patients in the intensive care unit (ICU). The timely assessment of new or rapidly evolving findings is critical. Optimal radiographic technique, availability of images to the clinicians, and rapid reporting by the radiologist all serve to maximize the efficacy of bedside chest radiography in the ICU. Sometimes, changes in cardiopulmonary status may only be appreciated on chest radiographs (CXRs). Complications from ventilatory assistance, such as barotrauma, occur frequently and must be detected promptly. The position of monitoring devices, an important component of critical care management, is best checked radiographically. Indications for CXRs and the recommended frequency for repeat follow-up CXRs are based on the existing literature and the consensus of an expert panel formed by the American College of Radiology.     

Residual masses after chemotherapy for metastatic testicular cancer: the clinical implications of the association between retroperitoneal and pulmonary histology. Re-analysis of Histology in Testicular Cancer (ReHiT) Study Group

PURPOSE: We determined the need and sequence of retroperitoneal lymph node dissection and thoracotomy in patients with nonseminomatous testicular cancer, and with residual retroperitoneal and pulmonary masses after chemotherapy. MATERIALS AND METHODS: We studied 159 patients undergoing retroperitoneal lymph node dissection and a thoracotomy following cisplatin based induction chemotherapy for metastatic testicular nonseminomatous germ cell tumor. Several well-known predictors for residual histology (necrosis, mature teratoma and cancer) were evaluated. RESULTS: As expected, necrosis was found more often at retroperitoneal lymph node dissection if the primary tumor was negative for teratoma, the residual mass was small or the decrease in size was great. Contrary, neither residual mass size nor the decrease in size was predictive of the histological status of the residual lung lesion. Histological findings in the retroperitoneum and lung were strongly correlated, such that necrosis at retroperitoneal lymph node dissection was associated with an 89% probability of necrosis in the lung. CONCLUSIONS: Retroperitoneal lymph node dissection should be performed before thoracotomy is considered, since the histological status at dissection is a strong predictor of that at thoracotomy.