Antibody seronegative human T-lymphotropic virus type III (HTLV-III)- infected patients with acquired immunodeficiency syndrome or related disorders

The human T-lymphotropic virus type III (HTLV-III) is the primary cause of the acquired immunodeficiency syndrome (AIDS) and related disorders (ARC). Prior studies have reported that nearly all symptomatic patients with AIDS or ARC manifest antibody to HTLV-III. This observation has engendered efforts to screen for HTLV-III, especially prior to blood donation, with assays for antibody to HTLV-III. We report the first two cases, one with AIDS and one with ARC, that are HTLV-III virus positive but antibody negative. Accurate diagnosis of HTLV-III infection in some cases may require direct virus culture or tests for antigen. In addition, lack of HTLV-III antibody may indicate an atypical clinical course of AIDS.     

Medial preoptic area involvement in norepinephrine-induced suppression of pulsatile luteinizing hormone release in ovariectomized rats

This study examined whether the medial preoptic area (MPOA) is a site which mediates the inhibitory effects of norepinephrine (NE) on pulsatile luteinizing hormone (LH) secretion in ovariectomized rats. Animals were bled continuously at a rate of 50 microliter whole blood/7 min for 2 h prior to push-pull perfusion in the MPOA, and during a 2-3 h period of perfusion of the MPOA (20 microliter/min) with artificial CSF, or 2 or 20 pg NE/min. In another group of rats LH levels were only determined during a 2-3 h period of MPOA perfusion with CSF. Pulsatile LH release was not affected by push-pull perfusion with CSF when a comparison was made to preperfusion LH values in the same rats. Moreover, LH levels obtained from rats only bled during MPOA perfusion with CSF were not different from LH values obtained during the preperfusion periods in the other groups. However, push-pull perfusion of the MPOA with 2 or 20 pg NE/min significantly suppressed mean LH levels by causing a 35-45% reduction in pulse frequency. No decrease occurred in LH pulse amplitude. Therefore, these studies demonstrate that NE acting at the level of the MPOA can suppress pulsatile LH release solely by decreasing LH pulse frequency.     

Estrogen and progesterone receptors in the human vagina

Estrogen (E) and progesterone (Pg) receptor (R) levels were determined in the human vagina in relation to menopausal status, day of ovarian cycle and pregnancy. The results obtained confirmed that the human vagina contains ER and, in addition, demonstrated for the first time the presence of PgR in this organ in humans. In cycling women, ER and PgR did not vary significantly during the ovarian cycle; however low (less than or equal to 10 fmoles/mg cytosol protein) concentrations of PgR were more frequently (6 out of 8 cases) detected during the secretory phase. No substantial difference was seen in ER and PgR values between anterior and posterior wall of the vagina. In postmenopausal patients the levels of ER (range: 10-83 fmoles/mg) were similar to those found in premenopause (range: 12-78 fmoles/mg). As regards PgR, the majority (14 out of 20) of vaginae were devoid of PgR, 4 had a very low (less than or equal to 6 fmoles/mg) PgR content and only 2 cases had a PgR level higher than 10 fmol/mg cytosol protein. In pregnant patients (6th to 8th week) ER were found in all vaginae, while PgR were present only in some cases (3 out of 8). It was concluded that the behavior of ER in the human vagina seems different from that in the human endometrium, since ER levels do not vary in relation to changes in the concentrations of sexual hormones in the circulation. On the contrary, PgR levels appear to depend on blood estradiol and progesterone concentration, as in other target tissues.     

A possible mechanism of psoralen phototoxicity not involving direct interaction with DNA.

Psoralens in combination with ultraviolet light (UVA; 320-400 nm) are used in the photochemical treatment of a variety of skin diseases including vitiligo, a skin depigmentational disorder, and psoriasis, a disease of accelerated epidermal cell proliferation. Although it is generally assumed that the major site of action of the psoralens is DNA, we have obtained evidence that another site may be the primary target for these compounds. We have identified specific, saturable, high-affinity binding sites for 8-methoxypsoralen on HeLa cells and have detected specific binding of 8-methoxypsoralen to four other human cell lines and five mouse cell lines. In HeLa cells, specific binding is reversible and independent of the ability of the compound to intercalate into DNA. In addition, binding sites become covalently modified by the psoralen after UVA exposure. Specific binding of 8-[methoxy-3H]methoxypsoralen constitutes 79% of the label bound to the cells. Scatchard analysis indicated two classes of psoralen binding sites: high-affinity sites with a Kd of 19 X 10(-9) M (1.8 X 10(5) sites per cell) and low-affinity sites with a Kd of 4 X 10(-6) M (7.1 X 10(6) sites per cell). Four structurally related psoralen analogs block 8-methoxypsoralen binding in a manner that parallels their biological activity. Based on these findings, we hypothesize that specific binding sites for psoralens on mammalian cells mediate, at least in part, psoralen-induced phototoxicity.     

Changes in nerve growth factor level and symptom severity following antibiotic treatment for refractory overactive bladder

Introduction and hypothesis

Overactive bladder (OAB) has a multifactorial aetiology, and for some women symptoms may be associated with chronic urothelial inflammation secondary to bacterial colonisation. One marker of such inflammation may be urinary nerve growth factor (NGF). We hypothesised that for women with OAB and urothelial inflammation, urinary NGF would be reduced following antibiotic therapy.

Methods

Women with overactive bladder and urodynamic diagnosis of detrusor overactivity who were refractory to anticholinergics, and had histological evidence of urothelial inflammation were treated with a 6-week course of rotating antibiotics. Urinary NGF was measured by ELISA before and after treatment. Three-day bladder diaries, the Patients’ Perception of Intensity of Urgency Scale, the King’s Health Questionnaire and the Patients’ Perception of Bladder Condition questionnaire were used to assess subjective and objective outcomes of therapy.

Results

Thirty-nine women with refractory DO were recruited. The NGF levels decreased significantly after antibiotic therapy (Wilcoxon signed rank test; p?=?0.015). There were significant improvements in daytime frequency, nocturia and urgency (p?<?0.05), and 74 % of women reported improvement in perception of their bladder condition.

Conclusions

Urinary NGF is responsive to antibiotic therapy. Women with refractory overactive bladder and elevated NGF may benefit from antibiotic treatment.     

Squamous cell carcinoma of the renal pelvis with stones and inferior vena cava infiltration. Case report

We report a rare case of a 50 year old man with renal squamous cell carcinoma (SCC) who first came to our attention with renal colic and fever not responding to antibiotic or analgesic treatment. He had a long history of kidney stones, but had not undergone any imaging in the last 5 years. Physical examination revealed tenderness and a palpable mass in the right flank and lumbar region. A whole body CT scan was performed, revealing an 11 cm mass in the right kidney infiltrating the inferior vena cava. There were areas of calcification within the mass and multiple stones within the renal pelvis. The tumor was considered unsuitable for resection according to radiological and clinical criteria. The mass was biopsied percutaneously under CT guidance and histological examination revealed squamous cell carcinoma of the renal pelvis. The patient was treated with neoadjuvant chemotherapy and embolization of the renal artery. He died one month after diagnosis. To our knowledge this is the second reported case in the world of renal SCC infiltrating the inferior vena cava and with kidney stones.     

Intraoperative Administration of Inhaled Carbon Monoxide Reduces Delayed Graft Function in Kidney Allografts in Swine

Ischemia/reperfusion injury and delayed graft function (DGF) following organ transplantation adversely affect graft function and survival. A large animal model has not been characterized. We developed a pig kidney allograft model of DGF and evaluated the cytoprotective effects of inhaled carbon monoxide (CO). We demonstrate that donor warm ischemia time is a critical determinant of DGF as evidenced by a transient (4–6 days) increase in serum creatinine and blood urea nitrogen following transplantation before returning to baseline. CO administered to recipients intraoperatively for 1 h restored kidney function more rapidly versus air‐treated controls. CO reduced acute tubular necrosis, apoptosis, tissue factor expression and P‐selectin expression and enhanced proliferative repair as measured by phosphorylation of retinol binding protein and histone H3. Gene microarray analyses with confirmatory PCR of biopsy specimens showed that CO blocked proinflammatory gene expression of MCP‐1 and heat shock proteins. In vitro in pig renal epithelial cells, CO blocks anoxia‐reoxygenation‐induced cell death while promoting proliferation. This large animal model of DGF can be utilized for testing therapeutic strategies to reduce or prevent DGF in humans. The efficacy of CO on improving graft function posttransplant validates the model and offers a potentially important therapeutic strategy to improve transplant outcomes.     

Renal hemodynamic response to maximal vasodilating stimulus in healthy older subjects

BACKGROUND: It is still unclear whether age per se is associated with preservation of renal functional reserve, that is, of the increase in glomerular filtration rate (GFR) induced by appropriate vasodilating stimulus. METHODS: To gain insights into this issue, we evaluated the renal response to a maximal vasodilating stimulus, represented by the combined infusion of mixed amino acid solution (AA) and dopamine at renal dose (D), in 10 young subjects (median age of 30 years, range of 19 to 32) and in 11 subjects of older age (median age of 67 years, range of 65 to 76). Two further age-matched groups of young (N = 15) and older (N = 11) living kidney donors underwent renal needle biopsy immediately before nephrectomy to perform semiquantitative scoring (0 to 3) of arteriosclerosis in intrarenal arteries. All of the study subjects were nonsmokers with healthy status proven by extensive diagnostic evaluation excluding any risk factor of renal dysfunction. RESULTS: Basal renal plasma flow (RPF) and GFR were proportionally lower in older subjects (RPF, 361 +/- 29 vs. 618 +/- 34 mL/min/1.73 m(2), P < 0.001; GFR, 79 +/- 4 vs. 127 +/- 5.8 mL/min/1.73 m(2), P < 0.001). After AA + D, a significant increase of RPF and GFR was observed in both groups, but the older subjects exhibited a smaller percentage increment (RPF, 25.5 +/- 4.8 vs. 42.4 +/- 5.8, P < 0.05; GFR, 19.6 +/- 5.7 vs. + 33.8 +/- 6.4, P < 0.05). Furthermore, the maximal vasodilating stimulus was not able to restore renal hemodynamics in older subjects to the level measured in young controls at baseline. Renal vascular resistances were higher (P < 0.05) in the older subjects both at baseline (0.19 +/- 0.02 vs. 0.09 +/- 0.004 mm Hg/mL/min) and after AA + D (0.14 +/- 0.01 vs. 0.06 +/- 0.004). Light microscopy examination detected the presence of a greater degree of arteriosclerosis at the level of interlobular and arcuate arteries (0.89 +/- 0.15 vs. 0.45 +/- 0.08) and interstitial fibrosis/tubular atrophy (1.18 +/- 0.13 vs. 0.53 +/- 0.13) in older than in young subjects. CONCLUSIONS: Therefore, aging has adverse effects on renal function despite the absence of any risk factor for renal disease, including chronic smoking: (1) GFR and RPF are lower, and (2) the renal response to maximal vasodilating stimulus is impaired. These aging-related alterations of renal hemodynamics are possibly due to organic lesions in renal vasculature.     

Analysis of MGMT promoter methylation status on intraoperative fresh tissue section from frameless neuronavigation needle biopsy: a preliminary study of ten patients

Background

After a brain biopsy, the genetic analysis can fail because of insufficient material, extensive tumor necrosis, and formalin fixation under conditions that adversely affected the quality of the DNA or because the assay result was indeterminant. The freezing of fresh tumor tissue at surgery could greatly improve the success of DNA extraction and methyl guanine methyl transferase (MGMT) promoter methylation testing. The concentration of the DNA samples can also be improved from a withdrawal in an area with a high probability of neoplastic cells.

Methods

The present study reports the results of ten frameless image-guided intracranial needle biopsies from April 2008 until February 2009, among a total of 28 frameless neuronavigation brain biopsy performed from May 2007 to February 2009. The protocol sampling provided withdrawal specimens correlated with neuroimaging characteristics of the lesions. The molecular determination of MGMT promoter was assessed with the nested methylation-specific polymerase chain reaction on fresh or cryopreserved needle bioptic tissue.

Results

The genetic characterization was feasible in all the bioptic samples. The MGMT promoter was methylated in six patients, including a brain infection. The image-guided trajectory of the biopsy and the intraoperative frozen section increased the diagnostic yield.

Conclusions

To the best of the authors' knowledge, this is the first report with the MGMT promoter status analysis on needle bioptic fresh tissue. In the future, the availability of the molecular genetic characterization of a brain tumor before open surgery will provide important information for the optimal treatment.