'Organic Anxiety' in a Middle-aged Man Presenting with Dyspnoea: a Case Report.

We report a case of pulmonary embolism in a patient who presented with repeated anxiety attacks and psychotic symptoms and was misdiagnosed as having withdrawal seizure or anxiety disorder not otherwise specified. This case highlighted the nonspecific clinical features of pulmonary embolism and the principles in making psychiatric diagnosis. Careful history taking, thorough physical examination, appropriate investigation, and a high index of suspicion led to the correct diagnosis. The principle of hierarchy of psychiatric diagnosis (ie, organic over non-organic) and the possibility of comorbidities should always apply.

Statistical analysis of whole-body absorption depending on anatomical human characteristics at a frequency of 2.1 GHz.

In this paper, we propose identification of the morphological factors that may impact the whole-body averaged specific absorption rate (WBSAR). This study is conducted for the case of exposure to a front plane wave at a 2100 MHz frequency carrier. This study is based on the development of different regression models for estimating the WBSAR as a function of morphological factors. For this purpose, a database of 12 anatomical human models (phantoms) has been considered. Also, 18 supplementary phantoms obtained using the morphing technique were generated to build the required relation. This paper presents three models based on external morphological factors such as the body surface area, the body mass index or the body mass. These models show good results in estimating the WBSAR (<10%) for families obtained by the morphing technique, but these are still less accurate (30%) when applied to different original phantoms. This study stresses the importance of the internal morphological factors such as muscle and fat proportions in characterization of the WBSAR. The regression models are then improved using internal morphological factors with an estimation error of approximately 10% on the WBSAR. Finally, this study is suitable for establishing the statistical distribution of the WBSAR for a given population characterized by its morphology.

Analysis of RF exposure in the head tissues of children and adults.

This paper analyzes the radio frequencies (RF) exposure in the head tissues of children using a cellular handset or RF sources (a dipole and a generic handset) at 900, 1800, 2100 and 2400 MHz. Based on magnetic resonance imaging, child head models have been developed. The maximum specific absorption rate (SAR) over 10 g in the head has been analyzed in seven child and six adult heterogeneous head models. The influence of the variability in the same age class is carried out using models based on a morphing technique. The SAR over 1 g in specific tissues has also been assessed in the different types of child and adult head models. Comparisons are performed but nevertheless need to be confirmed since they have been derived from data sets of limited size. The simulations that have been performed show that the differences between the maximum SAR over 10 g estimated in the head models of the adults and the ones of the children are small compared to the standard deviations. But they indicate that the maximum SAR in 1 g of peripheral brain tissues of the child models aged between 5 and 8 years is about two times higher than in adult models. This difference is not observed for the child models of children above 8 years old: the maximum SAR in 1 g of peripheral brain tissues is about the same as the one in adult models. Such differences can be explained by the lower thicknesses of pinna, skin and skull of the younger child models.

Variability analysis of SAR from 20 MHz to 2.4 GHz for different adult and child models using finite-difference time-domain.

This paper deals with the variability of body models used in numerical dosimetry studies. Six adult anthropomorphic voxel models have been collected and used to build 5-, 8- and 12-year-old children using a morphing method respecting anatomical parameters. Finite-difference time-domain calculations of a specific absorption rate (SAR) have been performed for a range of frequencies from 20 MHz to 2.4 GHz for isolated models illuminated by plane waves. A whole-body-averaged SAR is presented as well as the average on specific tissues such as skin, muscles, fat or bones and the average on specific parts of the body such as head, legs, arms or torso. Results point out the variability of adult models. The standard deviation of whole-body-averaged SAR of adult models can reach 40%. All phantoms are exposed to the ICNIRP reference levels. Results show that for adults, compliance with reference levels ensures compliance with basic restrictions, but concerning children models involved in this study, the whole-body-averaged SAR goes over the fundamental safety limits up to 40%.

Modeling of RF head exposure in children.

This study analyzes the main parameters that should influence the specific absorption rate (SAR) in children's heads. The evolution of their head shape and the growth of specific parameters, such as the skull thickness, are analyzed. The influence of these parameters on the radio frequency (RF) exposure of children's head is studied. The SAR over 1 g in specific tissue is assessed in different children's head models based on magnetic resonance imaging (MRI) and on non-uniformly down-scaled adult heads. Comparisons with SAR data in adults are reported using a handset with a patch antenna operating at 900 MHz.

Bacterial biosorbent for removing and recovering copper from electroplating effluents.

Investigations were carried out to study the removal and recovery of Cu(II) ions from wastewater by Micrococcus sp. The Langmuir isotherm model described very well the equilibrium behavior of copper biosorption, with maximum biosorption capacity (q(max)) reaching 52.1 mg Cu2+/g dry cell at pH 6. Biomass prewashed with sulfuric acid (0.05 mol 1(-1)) and sodium sulfate (1 mol l(-1)) solutions were shown to increase the copper removal capabilities up to 27% and 16%, respectively. Copper uptake by cells was negligible at pH 2.0 and then increased quickly with increasing pH until 6.0. Cells of Micrococcus sp. were immobilized in 2% calcium alginate and 10% polyacrylamide gel beads. A counter-current process comprising a series of immobilized cell reactors was developed for removing and recovering copper from electroplating effluents. This process was capable of producing an effluent at low copper concentration, with only a minimum amount of desorbing agent used. The technique of scanning electron microscopy coupled with X-ray dispersion analysis shows that Cu2+ exchanged with K+ and Ca2+ on the cell wall of Micrococcus sp., thereby suggesting ion exchange as one of the dominant mechanisms of metal biosorption for this bacterial strain.

Removal and recovery of copper (II) ions by bacterial biosorption.

Studies were conducted to investigate the removal and recovery of copper (II) ions from aqueous solutions by Micrococcus sp., which was isolated from a local activated sludge process. The equilibrium of copper biosorption followed the Langmuir isotherm model very well with a maximum biosorption capacity (q(max)) of 36.5 mg of Cu2+/g of dry cell at pH 5.0 and 52.1 mg of Cu2+/g of dry cell at pH 6.0. Cells harvested at exponential growth phase and stationary phase showed similar biosorption characteristics for copper. Copper uptake by cells was negligible at pH 2.0 and then increased rapidly with increasing pH until 6.0. In multimetal systems, Micrococcus sp. exhibited a preferential biosorption order: Cu approximate to Pb > Ni approximate to Zn. There is virtually no interference with copper uptake by Micrococcus sp. from solutions bearing high concentrations of Cl-, SO4(2-), and NO3- (0-500 mg/L). Sulfuric acid (0.05 M) was the most efficient desorption medium, recovering >90% of the initial copper sorbed. The copper capacity of Micrococcus sp. remained unchanged after five successive sorption and desorption cycles. Immobilization of Micrococcus sp. in 2% calcium alginate and 10% polyacrylamide gel beads increased copper uptake by 61%. Biomass of Micrococcus sp. may be applicable to the development of potentially cost-effective biosorbent for removing and recovering copper from effluents.

Chemopreventive activity of a C-glucuronide analog of N-(4-hydroxyphenyl) retinamide-O-glucuronide against mammary tumor development and growth.

The long term chemopreventive effects of the N-(4-hydroxyphenyl) retinamide-O-glucuronide (4-HPROG), and its stable C-linked benzyl glucuronide analog, retinamidobenzyl glucuronide (4-HPRCG) on the growth and development of 7,12-dimethylbenz[a]anthracene-induced mammary tumors were compared. The retinamidobenzyl glucuronide is stable toward acid hydrolysis and resists the actions of beta-glucuronidase. The results indicate that the C-linked glucuronide analog, 4-HPRCG has a greater chemopreventive potency than an equimolar concentration of 4-HPROG. Tumor latency was 15% longer in rats fed 2 mmol/kg diet of 4-HPRCG as compared to 4-HPROG. At 80 days post DMBA-intubation, tumor incidence was 57% and 27% in the 4-HPROG and 4-HPRCG treated rats, respectively. Tumor multiplicity was also markedly decreased in the 4-HPRCG treated rats. At 80 days post DMBA intubation the control rats had an average of 1.43 tumors/rat compared to 0.71 and 0.36 tumors/rat in the 4-HPROG and 4-HPRCG respectively. The higher potency and low toxicity of 4-HPRCG suggest that this stable analog may have an in vivo chemopreventive advantage over its analog, 4-HPROG. The results also demonstrated that these glucuronide analogs do not bind effectively in vitro either to the nuclear retinoid receptors or to the cellular retinoid binding proteins. Regardless of the mode of action of these retinoids, they are clearly effective chemopreventive agents.

Urinary incontinence among female soldiers.

A self-administered questionnaire was developed to assess the prevalence of urinary incontinence among active duty female soldiers. The questionnaire also addressed basic demographic information, including height, age, weight, and the subjects' present and past military activities. Adaptive measures that the soldiers commonly used to continue exercising and perform their duties were also explored. Seven hundred thirteen questionnaires were handed out to female soldiers at Fort Lewis (Washington), Fort Benning (Georgia), and Fitzsimons Army Medical Center (Colorado) during preparation for physical fitness tests. Of the 563 soldiers (79%) who returned completed questionnaires, 31% indicated that they commonly experienced urinary incontinence during duty and/or training to the extent that it interfered with job performance, hygiene, or was socially embarrassing. Thus, urinary incontinence is a pervasive problem among female soldiers.

Diabetes insipidus in neurosurgical patients.

Diabetes insipidus (DI) is an uncommon but important complication in the neurosurgical population. This retrospective study aimed to determine the incidence, profile and outcome of patients admitted to an 18-bedded neurosurgical intensive care unit who developed DI. The overall incidence was 3.7% (29/792 admissions). Aetiologies included subarachnoid haemorrhage (12/29), severe head injury (11/29), post-surgical excision of craniopharyngioma or pituitary adenoma (5/29) and acute haemorrhagic stroke (1/29). All patients were treated with a regime of fluid replacement, electrolyte correction, parenteral or intranasal desmopressin (DDAVP), or parenteral pitressin. Overall mortality was 72.4%. There were no deaths in the patients who underwent excision of tumours. Complications included acute pulmonary oedema, hypernatremia and hypokalaemia. The development of DI was found to be associated with impending brain death and mortality in the majority of patients with subarachnoid haemorrhage and severe head injury. However, careful diagnosis and management of DI after hypothalamo-neurohypophyseal surgery did not result in any permanent neurological sequelae.

Behavioral treatment of exercise-induced urinary incontinence among female soldiers.

One-third of 450 female soldiers surveyed indicated that they experienced problematic urinary incontinence during exercise and field training activities. The other crucial finding of this survey was probably that 13.3% of the respondents restricted fluids significantly while participating in field exercises. Although only 5.3% of respondents felt that their urine leakage had a significant impact on their regular duties, it is obvious that many more are sufficiently worried about leakage to put themselves at significant risk for dehydration-related injuries. This study tested whether behavioral interventions effective among older people could help younger soldiers. Thirty-nine female soldiers reporting exercise-induced urinary incontinence underwent urodynamic assessments of bladder capacity, urethral closure pressure, and detrusor contraction pressures as well as a symptom questionnaire before and after therapy. They were stratified by diagnosis of physical stress incontinence or mixed urge/stress incontinence and randomized into two groups. Twenty-three participants performed pelvic muscle exercises with urethral biofeedback for 8 weeks, and 16 participants performed pelvic muscle exercises alone. Patient reports as well as the post-treatment examinations indicated that all subjects improved significantly. Only five subjects in the biofeedback/exercise and three in the exercise-only group desired further treatment. All subjects initially diagnosed with detrusor dysfunction had normal readings at the end of the study. Thus, behavioral treatments can be effective against exercise-induced urinary incontinence among most female soldiers.

Tracheostomy in a neuro-intensive care setting: indications and timing.

A retrospective review was made of 49 survivors who were mechanically ventilated for more than 48 hours in the neurosurgical ICU. Thirty-two patients (Gp I) were successfully extubated, 9 patients (Gp II) underwent tracheostomy after one or more failed extubations, and 8 patients (Gp III) underwent elective tracheostomy. Glasgow Coma Scale (GCS) scores at extubation were 11.3 +/- 2.8 (mean (SD) for Gp I vs 7.8 +/- 2.7 for Gp II (P = n.s.) and at elective tracheostomy (Gp III) was 5.4 +/- 2.3. Incidence of ventilator-associated pneumonia were 35% in Gp I vs 100% of patients in Gp II and III (P < 0.05). Reasons for reintubation in 7 of 9 patients (Gp II) were upper airway obstruction and tenacious tracheal secretions while 14 of 17 patients were weaned off the ventilator within 48 hours of tracheostomy. The length of stay in ICU was 16.8 +/- 7.1 days in Gp II vs 11.7 +/- 2.9 days in Gp III (P < 0.05). In our study, elective tracheostomy for selected patients with poor GCS scores and nosocomial pneumonia has resulted in shortened ICU length of stay and rapid weaning from ventilatory support.

Synthesis of naphthalenesulfonic acid small molecules as selective inhibitors of the DNA polymerase and ribonuclease H activities of HIV-1 reverse transcriptase.

Over 25 selected naphthalenesulfonic acid derivatives were evaluated for their inhibitory effect on two different functional domains of the HIV-1 reverse transcriptase (RT), namely the ribonuclease H and DNA polymerase activities. Most of the analogues were found to be either specific toward the DNA polymerase activity or showed nonselective inhibition of both catalytic functions. The most active compounds are either symmetrical derivatives or nonsymmetrical derivatives containing a lipophilic appendage consisting of a palmitoyl or cholesteryl moiety. The six most active compounds in the preliminary screen, derivatives 6, 16, 17, 23, 26, and 27, were subjected to experiments to determine their 50% inhibitory concentration (IC50) values in the assays that measure RNA-dependent DNA polymerase (RDDP), DNA-dependent DNA polymerase (DDDP), and ribonuclease H (RNase H) functions of HIV-1 RT. The most potent derivative was a nonsymmetric cholesterol-linked 4-amino-5-hydroxy-2,7-naphthalenedisulfonic acid analogue, compound 23, which demonstrated an IC50 value of 0.06 microM for inhibiting RDDP activity. Inhibition of DDDP and RNase H activity for this compound was demonstrated at concentrations that were over 100-fold of that for inhibiting RDDP activity. However, the potency of this active compound does not correlate in the whole virus assay, probably due to a lack of cellular entry. The cholesterol derivative, 23, also possesses HIV-1 protease inhibitory activity and belongs to a unique class of multifunctional HIV-1 inhibitors.

Inactivation of hepatitis C virus in low pH intravenous immunoglobulin.

The safety from hepatitis C virus of intravenous immunoglobulin prepared by the cold ethanol method of Cohn-Oncley is demonstrated by clearance through the manufacturing process of 9 x 10(6) plaque-forming units of bovine viral diarrhea virus used as a surrogate for hepatitis C virus. Incubation of the intravenous immunoglobulin in its final formulation at pH 4.25 for 21 days at 21 degrees C caused a 10,000-fold decrease in bovine viral diarrhea virus intentionally added and complete inactivation of 1000 chimpanzee infectious doses per ml of hepatitis C virus.

Structure-activity relationship studies with symmetric naphthalenesulfonic acid derivatives. Synthesis and influence of spacer and naphthalenesulfonic acid moiety on anti-HIV-1 activity.

Symmetric bis(naphthalenesulfonic acid) derivatives containing a variety of spacers have been synthesized and evaluated for anti-HIV-1 activity in four assay systems. In the assay that measured inhibition of HIV-1-induced cytopathogenicity using a laboratory strain (HTLV-IIIB), a hexamethylene and octamethylene spacer derivative of 4-amino-5-hydroxy-2,7-naphthalenedisulfonic acid emerged as the most potent derivatives. The hexamethylene spacer analog exhibited an in vitro therapeutic index that was > 120. Selected derivatives were tested in the giant cell formation assay. In this assay, the most potent derivative was, again, the hexamethylene compound. Evaluation of selected derivatives against a clinical isolate of HIV-1 (HE strain) revealed that the hexamethylene derivative was the most potent compound. In the assay that measured the inhibition of HIV-1-induced cytopathogenesis in human peripheral blood lymphocytes, the hexamethylene compound emerged as the most active derivative, demonstrating a 50% inhibitory concentration of 1.3 microM. These studies clearly demonstrate that certain naphthalenesulfonic acid moieties when coupled to specific spacers were synergistic in producing anti-HIV-1 activity at nontoxic concentrations. In the 4-amino-5-hydroxy-2,7-naphthalenedisulfonic acid series, shortening of the spacer length, preferably with a flexible polymethylene chain, was highly beneficial for increasing anti-HIV-1 potency.

Fungus-specific translation elongation factor 3 gene present in Pneumocystis carinii.

Historically, Pneumocystis carinii pneumonia has been the most frequent cause of morbidity and mortality in patients with AIDS. Antiprotozoan drugs are effective in the treatment and prophylaxis of P. carinii pneumonia, which lends credence to the widely held view that P. carinii is a protozoan. However, recent genetic evidence suggests that P. carinii should be classified as a fungus. Translation elongation factor 3 (EF-3) is an essential, soluble translation component which is unique to fungal protein synthesis and is not required for protein synthesis in other eukaryotes. We have identified and isolated a gene for EF-3 from P. carinii, adding more evidence for this organism's assignment as a fungus.

A mutant poliovirus containing a novel proteolytic cleavage site in VP3 is altered in viral maturation.

A six-amino-acid insertion containing a Q-G amino acid pair was introduced into the carboxy terminus of the capsid protein VP3 (between residues 236 and 237). Transfection of monkey cells with full-length poliovirus cDNA containing the insertion described above yields a mutant virus (Sel-1C-02) in which cleavage occurs almost entirely at the inserted Q-G amino acid pair instead of at the wild-type VP3-VP1 cleavage site. Mutant Sel-1C-02 is delayed in the kinetics of virus production at 39 degrees C and exhibits a defect in VP0 cleavage into VP2 and VP4 at 39 degrees C. Sucrose gradient analysis of HeLa cell extracts prepared from cells infected by Sel-1C-02 at 39 degrees C shows an accumulation of fast-sedimenting replication-packaging complexes and a significant amount of uncleaved VP0 present in fractions containing mature virions. Our data provide in vivo evidence for the importance of determinants other than the conserved amino acid pair (Q-G) for recognition and cleavage of the P1 precursor by proteinase 3CD and show that an alteration in the carboxy terminus of VP3 or the amino terminus of VP1 affects the process of viral maturation.

Detection and reduction of protein A contamination in immobilized protein A purified monoclonal antibody preparations.

Protein A chromatography is an excellent technique for the purification of monoclonal antibodies. However, the presence of Protein A in therapeutic monoclonal antibody preparations due to leaching has been linked with toxicity in animals and humans. Two sandwich ELISAs were developed to monitor Protein A column leaching: (1) rabbit anti-Protein A for capture and anti-Protein A F(ab')2-HRP for detection; and (2) rabbit anti-Protein A for capture and anti-Protein A-biotin for detection. The biotin ELISA is sensitive to the subnanogram range. In addition, these assays were used to develop DEAE and gel filtration chromatography techniques that substantially reduce Protein A levels in monoclonal antibodies purified by Protein A chromatography.

Virus inactivation/elimination in therapeutic protein concentrates.

Concern for virus transmission from intravenous biological products, derived from natural and biotechnological sources, has prompted us to investigate various methods for virus inactivation while preserving the biological activity of the therapeutic entity. This concern is currently acute regarding the presence of HIV in purified human plasma protein concentrates. Four different methods of virus removal (1) heating in solution; (2) use of lipid solvents; (3) low pH treatment, and (4) partitioning during purification, are reported for various plasma proteins that have been spiked with model viruses. General virus inactivation strategies for therapeutic protein concentrates are discussed.