Chronic prenatal exposure to carbon monoxide results in a reduction in tyrosine hydroxylase-immunoreactivity and an increase in choline acetyltransferase-immunoreactivity in the fetal medulla: implications for Sudden Infant Death Syndrome

Maternal cigarette smoking during pregnancy is associated with a significantly increased risk of Sudden Infant Death Syndrome (SIDS). This study investigated the effects of prenatal exposure to carbon monoxide (CO), a major component of cigarette smoke, on the neuroglial and neurochemical development of the medulla in the fetal guinea pig. Pregnant guinea pigs were exposed to 200 p.p.m CO for 10 h per day from day 23-25 of gestation (term = 68 days) until day 61-63, at which time fetuses were removed and brains collected for analysis. Using immunohistochemistry and quantitative image analysis, examination of the medulla of CO-exposed fetuses revealed a significant decrease in tyrosine hydroxylase-immunoreactivity (TH-IR) in the nucleus tractus solitarius, dorsal motor nucleus of the vagus (DMV), area postrema, intermediate reticular nucleus, and the ventrolateral medulla (VLM), and a significant increase in choline acetyltransferase-immunoreactivity (ChAT-IR) in the DMV and hypoglossal nucleus compared with controls. There was no difference between groups in immunoreactivity for the m2 muscarinic acetylcholine receptor, substance P- or met-enkephalin in any of the medullary nuclei examined, nor was there evidence of reactive astrogliosis. The results show that prenatal exposure to CO affects cholinergic and catecholaminergic pathways in the medulla of the guinea pig fetus, particularly in cardiorespiratory centers, regions thought to be compromised in SIDS.     

Pseudoaneurysm of the medial inferior genicular artery following anterior cruciate ligament reconstruction

Pseudoaneurysm is a rare complication of surgery or trauma around the knee. A 30-year-old man presented 10 days following anterior cruciate ligament repair with a 2 cm pulsatile swelling on the medial side of the knee. Angiography demonstrated a pseudoaneurysm of the medial inferior genicular artery. Surgical exploration and ligation of the feeding vessel to the aneurysm was performed and the patient made a full recovery. Vascular injury must be suspected in patients presenting with a haemarthrosis or pulsatile swelling following surgery on the knee.     

A phase I trial of ZD9331, a water-soluble, nonpolyglutamatable, thymidylate synthase inhibitor.

PURPOSE: ZD9331 is a novel, direct-acting antifolate cytotoxic that does not require polyglutamation for activity, and is a specific thymidylate synthase inhibitor. This Phase I trial aimed to determine the maximum tolerated dose of ZD9331, given as a 30-min i.v. infusion on days 1 and 8 of a 21-day cycle. Pharmacokinetic parameters and tumor response were also assessed. EXPERIMENTAL DESIGN: A total of 71 patients, with a range of solid malignancies and refractory to standard therapies (44% had received > or =3 prior chemotherapy regimens), were treated. The most common malignancies were colorectal cancer (35% of patients) and ovarian cancer (31%). ZD9331 was escalated from 4.8 mg/m(2)/day. RESULTS: Dose-limiting toxicity occurred at 162.5 mg/m(2) ZD9331, with grade 4 thrombocytopenia, grade 4 neutropenia lasting > or =7 days, and grade 3 nonhematologic toxicity. Plasma clearance of ZD9331 was slow and dose-dependent; however, ZD9331 pharmacokinetics were nonlinear. Pharmacodynamics of ZD9331 were determined by measurement of plasma deoxyuridine, which increased at all of the dose levels; dose-related increases in plasma deoxyuridine were significant (P = 0.003) on day 5. Stable disease was observed in 37% of patients; 23% of ovarian cancer patients had a > or =50% reduction in CA125 levels. CONCLUSIONS: The maximum tolerated dose of this schedule was 130 mg/m(2). The toxicity profile at this dose was acceptable, with 7 of 28 patients treated developing grade 3/4 neutropenia and thrombocytopenia, 2 grade 4 diarrhea, and 2 grade 3/4 rash. This schedule was convenient and demonstrated activity in extensively pretreated patients; therefore, this is the recommended dose for study in Phase II trials.     

Efficacy of follow-up and contact tracing of women who test positive for genital tract chlamydia trachomatis prior to pregnancy termination.

We examined the efficacy of follow-up, contact tracing and the need for retreatment in women who were screen-positive for genital tract Chlamydia trachomatis prior to termination of pregnancy. Eighty-six of 1363 (6.3%) women screened positive. These women were significantly younger than those who screened negative (P < 0.0001). The genitourinary medicine (GUM) clinic was notified of 73 (84.9%) screen-positive women and 41 (47.7%) attended for follow-up. Contact tracing was undertaken in 38 (92.7%) women who attended and 29 (70.7%) women who attended required retreatment for Chlamydia. The median duration between pregnancy termination and GUM clinic attendance was significantly longer in women who required retreatment compared to those who did not require retreatment (P = 0.003). In conclusion, follow-up and contact-tracing of women who screen positive for genital tract C. trachomatis was incomplete. This may substantially compromise the cost-effectiveness of a screen-and-treat programme.     

Erectile dysfunction

A 63 year old man comes to you for a routine check of hisblood pressure.During the consultation you notice an entry in hisnotes about difficulty with erections that was never followed up.What issues you should coverIs this an ongoing problem?-Healthcare professionalsoften fail to initiate discussion of possible erectile dysfunction,whether because of embarrassment,lack of knowledge,orpressure of time.Patients find it even more difficult to raise theissue with their doctors,even though erectile dysfunction can     

Experience of combined endoscopic percutaneous stenting with ultrasound guidance for drainage of pancreatic pseudocycts

The therapeutic options for treatment of pancreatic pseudocysts are numerous. We report our experience of combined endoscopic and ultrasound guided percutaneous stenting for pancreatic pseudocysts. Data were prospectively collected for 20 consecutive patients. All patients had undergone a standard technique of combined endoscopic and ultrasound guided percutaneous placement of double J stents, between a pancreatic pseudocyst and the stomach. Patients age ranged between 25 and 84 years. Thirteen of the pseudocysts were due to acute pancreatitis and 7 were due to chronic pancreatitis. The duration of the combined procedure was mean 50 min (range 30-95 min). The length of hospital stay was mean 5 days (range 2-77 days. Only two patients suffered postoperative complications; one was re-admitted 2 weeks following stenting with acute cholecystitis, the other suffering a perforated duodenal ulcer 3 weeks after stenting. There were two failures early in the series, both due to stent migration, these stents were of a small size, (4.7 French). Following this the stent size was increased to at least 7 French, no further failures occurred. There was no operative mortality for the series. Follow-up ranged between 6 months and 5 years. We conclude that a combined percutaneous and endoscopic cyst-gastrostomy stent is a safe and effective treatment for patients with suitably placed pseudocysts.     

Analysis of vesicle fluid following the sting of the lionfish Pterois volitans

P. S. , H. E. , R. S. and J. P. . Analysis of vesicle fluid following the sting of the lionfish Pterois volitans. Toxicon 25, 1350 – 1353, 1987. — Fluid aspirated from blisters following a lionfish (Pterois volitans) sting was analyzed utilizing combined capillary column gas chromatography and negative ion chemical ionization mass spectrometry. Analysis for prostaglandin F₂ demonstrated 16.91 ng/ml, for prostaglandin E₂ 0.143 ng/ml, for 6-keto-prostaglandin F₁ less than 0.1 ng/ml (nondetectable) and for thromboxane B₂ 1.65 ng/ml. Platelet aggregation studies showed that blister fluid caused aggregation of isolated platelets only, which was inhibited by heat treatment or by the presence of normal donor plasma.     

Improved design of nasogastric feeding tubes

Disappointed with the overall performance of weighted and unweighted nasogastric feeding tubes, a design programme was initiated which resulted in the development of two new nasogastric tubes, one weighted and one unweighted. The tubes were manufactured with polyurethane rather than polyvinylchloride (PVC) which permitted an increase in diameter of the internal lumen which in turn was coated with water activated lubricant to ease removal of the introducer wire. A specially modelled outflow port was incorporated into the tips of both tubes. The performance of the two new polyurethane nasogastric feeding tubes was assessed under controlled trial condition using as a reference a widely used PVC unweighted open ended tube. While intubation times were similar in patients without concurrent endotracheal intubation, it took a significantly shorter time to intubate patients with concurrent endotracheal intubation with the new weighted tube. Following tube intubation, it was possible to aspirate gastric contents significantly more often through the new polyurethane tubes (p < 0.001) than through the PVC tube, and the unweighted polyurethane tube stayed in situ longer (p < 0.05) than the PVC tube. The newly designed polyurethane nasogastric feeding tubes are the first tubes that have been shown to have advantages over the simpler type of open ended, unweighted PVC nasogastric feeding tubes.     

Dynamic properties of the responses of single neurons in the inferior colliculus of the rat

The responses of single cells in the central nucleus of the inferior colliculus of the rat were studied with characteristic frequency tones amplitude modulated by pseudorandom noise or sinusoidal waveforms, in order to investigate the degree to which these responses can be described by a linear model. When pseudorandom noise was used as the modulating waveform, period histograms of the response locked to the periodicity of the noise were cross-correlated with a single period of the noise. The response of a model, having this cross-correlogram as its impulse response and the pseudorandom noise sequence as the input waveform, differed in appearance from the corresponding period histogram of the neural discharges, indicating that the latter contained a non-negligible, nonlinear component. Further manipulation of the data showed that the most significant nonlinearities were of even order, which indicates that the changes in neural discharge rate to increments and decrements in stimulus intensity are asymmetrical. In some units, particularly at low mean stimulus intensities, this was clearly evident as a halfwave rectification of the period histogram. The magnitude of the modulation of the period histograms increased as a function of the sound intensity for some units, while in others it decreased; in still other units the magnitude of the modulation of the neural discharges was relatively constant over a large range of stimulus intensities. When the modulation transfer functions were estimated from the responses to noise-modulated sounds they were found to be very similar to those obtained using sinusoidally modulated sound, despite large degrees of nonlinearity being present in the responses to both types of sound.     

Cell surface expression of epidermal growth factor receptor and Her-2 with nuclear expression of Her-4 in primary osteosarcoma

There is controversy over the role of Her-2 in osteosarcoma, with some investigators reporting association between expression and adverse outcome, whereas others point to the lack of gene amplification and membranous expression by immunohistochemistry (IHC) as inconsistent with biological significance. Her-2 normally requires pairing with epidermal growth factor receptor (EGFR), Her-3, or Her-4, but these have been less well studied in osteosarcoma. We evaluated the expression of each of these receptors in osteosarcoma and their potential to contribute to pathogenesis by examining a panel of low-passage primary osteosarcoma cell lines, comparing these with archival tumor specimens. Her-2 immunoreactivity was seen frequently in the diffuse staining pattern described previously. We observed EGFR in all samples by IHC. Her-3 expression was not observed. Her-4 expression was nuclear in distribution in all tumor samples and many cell line samples, consistent with activation and cleavage of the receptor. Quantified expression of Her-2 and EGFR mRNA by quantitative, real-time PCR in cell lines correlated with IHC for Her-2 but not for EGFR. Western blot identified full-length receptors for EGFR and Her-2 in all expected cell lines and showed Her-4 to be predominantly in the p80 form. Flow cytometry identified cell surface Her-2 and EGFR in all lines with receptor expression by IHC. We conclude that the cell surface expression of Her-2 and EGFR and the nuclear localization of the activated p80 fragment of Her-4 suggest that all three may be contributing to osteosarcoma pathogenesis. Therapy directed against this family of receptors may be beneficial for patients with osteosarcoma.