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Biomedical subjects

J Cohen

Publications and source records attributed to J Cohen.

At least 55 records · Page 3Linked to original sources

Assessment of adrenocortical function in the critically ill.

OBJECTIVE: To review current concepts in the diagnosis of adrenocortical disease in the critically ill patient. DATA SOURCES: A review of articles reported on adrenocortical insufficiency in the acutely ill patient. SUMMARY OF REVIEW: The contribution of adrenal insufficiency to the morbidity of critically ill patients is currently under renewed scrutiny. The debate continues about the role of steroids in sepsis and essentially the question remains unanswered. Central to this debate is the issue of whether adrenal insufficiency is common in the critically ill patient. What is incontrovertible is that adrenocortical function is essential for host survival during critical illness, but what constitutes adrenocortical insufficiency in critically ill patients is not clear. Absolute adrenocortical insufficiency (diagnosed by very low plasma cortisol concentrations) is uncommon in the intensive care population. The diagnosis of relative adrenocortical insufficiency (elevated basal plasma cortisol with a subnormal increase in plasma concentrations following an ACTH stimulus) continues to generate debate. The controversy surrounding the role of steroids in sepsis and the confusion over the criteria for diagnosing adrenal insufficiency in the critically ill are reviewed. CONCLUSIONS: We suggest that the following caveats be borne in mind when diagnosing adrenal insufficiency in the critically ill patient. Firstly, the gold standard for the diagnosis has not been established. Secondly, caution must be exercised when interpreting a single plasma cortisol value. In the event of a single result indicating adrenal hypofunction, we suggest repeating the measurements after a 6 to 12 hour interval. The clinician must also be aware of variations in cortisol concentrations induced by the assay. Thirdly, the clinician must be aware of the potential limitations of the conventional high dose corticotrophin test. We also suggest that plasma free cortisol is more relevant than total plasma cortisol in the assessment of adrenal function in critical illness and that the low dose corticotrophin test is more sensitive than the conventional high dose test. These areas should be the subject of further investigations.

Journal Article↗

Characterization of a distinct carlavirus isolated from Verbena.

Avirus was isolated from Verbena plants that bore virus-like symptoms. The virus, for which the name Verbena latent virus (VeLV) is proposed, was consistently isolated from these plants, both with and without disease symptoms. Electron microscopy studies of ultrathin sections of infected Verbena tissues revealed the presence of elongated flexuous virus particles, ca. 650 nm in length. Its experimental host range was limited to Verbena spp. and Nicotiana clevelandii. No inclusion bodies or specific cytopathological effects, were observed. Electrophoresis of dissociated purified virus preparation in sodium dodecyl sulfate-polyacrylamide gel revealed a major protein component with a molecular mass of 38.9 kDa. Polyclonal antibodies which could specifically bind to virus particles were produced. A portion of the viral RNA was cloned and sequenced; it comprised 2503 nucleotides and contained part of three open reading frames (ORFs) which from the 5' to the 3'-ends, potentially encode for 489 amino acids (ORF1), a 25.8-kDa protein (ORF2) and a 12-kDa protein (ORF3). Comparison of the predicted amino acid sequence with those of other plant viruses revealed 40-60% identity with several carlaviruses. In the light of particle morphology, absence of specific cytopathological effects in ultrathin sections, and genomic and serological properties, it is suggested that this virus belongs to the genus Carlavirus.

Amino Acid Sequence↗

Epilepsy and migraine.

Migraine and epilepsy are both chronic disorders characterized by recurrent neurologic attacks variously accompanied by headache as well as by gastrointestinal, autonomic, and psychologic features. Migraine and epilepsy are linked by their symptom profiles, comorbidity, and treatment. The presence of one disorder increases the likelihood that the other is also present. In addition, a number of migraine syndromes can be confused with epilepsy. The diagnosis and treatment of each disorder must take into account the potential presence of the other. Herein, we review the relationship between migraine and epilepsy. We discuss the diagnosis of migraine using the International Headache Society criteria, emphasizing the variants of migraine most frequently mistaken for epilepsy. We summarize the epidemiologic evidence that migraine and epilepsy are associated and discuss specific interrelationships between migraine and epilepsy.

Comorbidity↗

A prospective study of fever in the accident and emergency department.

Body temperature is one of the most commonly performed measurements in the accident and emergency department, and is often used as the basis for clinical decisions. Fever is frequently assumed to indicate infection, but there are few data on unselected patients presenting acutely. We studied 101 consecutive patients with fever (temperature (38 degrees C) among 3991 presentations to two emergency departments in tertiary-care inner city hospitals. The commonest categorical discharge diagnosis, or diagnosis at seven days, was infection (63%). There were no simple clinical tests that could distinguish fever due to infection from other diagnoses. The results suggest that, for patients presenting to an emergency department, pyrexia often indicates infection that may necessitate admission, especially in the elderly.

Accidents↗

A prospective, double-blind, randomized, parallel- group, dose-ranging study of botulinum toxin type a in female subjects with horizontal forehead rhytides.

BACKGROUND: Botulinum toxin type A is used cosmetically to improve facial lines, but it has not been thoroughly investigated for the treatment of horizontal forehead rhytides. OBJECTIVE: To compare the efficacy and safety of three doses of botulinum toxin type A in females with horizontal forehead rhytides and to establish whether the response rate and the duration of response are dose dependent. METHODS: Fifty-nine female patients with horizontal forehead rhytides scoring 2 (moderate) or 3 (severe) on the facial wrinkle scale (FWS) were randomly assigned to receive 16, 32, or 48 U of botulinum toxin type A (BOTOX, BOTOX Cosmetic; Allergan, Irvine, CA), which was administered to eight injection sites. Half of the dose was administered to the brow depressors and the other half to the elevators. Wrinkle severity was assessed by the investigator and patient using the FWS at baseline, at Weeks 2 and 4, and then every 4 weeks for 48 weeks. RESULTS: Improvements in horizontal rhytides were observed in all dosage groups. Significant dose-response trends were observed for rate of improvement at maximum brow elevation (53% in the 48-U group vs. 15% in the 16-U group at 16 weeks) and rate of relapse to baseline (35% in the 48-U group vs. 75% in the 16-U group at 16 weeks) by a trained observer. CONCLUSION: Higher botulinum toxin type A doses resulted in greater efficacy and longer duration of effect in the reduction of horizontal rhytides.

Adolescent↗

Taskforce 5: preimplantation genetic diagnosis.

The European Society of Human Reproduction and Embryology (ESHRE) Ethics Task Force sets out a recommended multidisciplinary approach to the application of preimplantation genetic diagnosis (PGD). The statement includes consideration of fundamental ethical principles, specific problems in cases of high genetic risk, and PGD for aneuploidy screening, HLA typing and sex selection for non-medical reasons.

Aneuploidy↗

Children conceived using ICSI do not have an increased risk of delayed mental development at 5 years of age.

BACKGROUND: Concerns about possible adverse outcomes for children conceived using ICSI were highlighted in 1998 when 1-year-old ICSI children were found to be at increased risk (relative risk = 9.2) of delayed mental development compared with children conceived naturally or using IVF. As the findings were biologically plausible, it was considered important to reassess child development when a more accurate measure of long-term cognitive ability could be obtained. METHODS: The mental development of 97 ICSI, 80 IVF and 110 naturally conceived (NC) children at 5 years of age was assessed using intelligence quotients (IQ) obtained from the Wechsler Preschool and Primary Scales of Intelligence. RESULTS: The mean full-scale IQ was 110 +/- 18 for ICSI, 111 +/- 13 for IVF and 114 +/- 13 for NC children (P = 0.21, non-significant). ICSI children were not at increased risk for delayed (full-scale IQ <85) cognitive development (ICSI 5.2%, IVF 2.5%, NC 0.9%; P = 0.18, non-significant). The only significant independent predictor of below-average full-scale IQ on multivariate analysis was lower maternal education level. CONCLUSIONS: These findings suggest that the genetic influence of parental cognitive ability is more important than the mode of conception in determining the long-term intellectual ability of children conceived using ICSI.

Case-Control Studies↗

Functional and fluorochrome analysis of an exocytotic mutant yields evidence of store-operated Ca2+ influx in Paramecium.

A non-discharge mutant of Paramecium tetraurelia (nd12-35 degrees C, lacking exocytotic response upon stimulation with the nonpermeable polycationic secretagogue aminoethyldextran, AED), in the pawnA genetic context (d4-500r, lacking ciliary voltage-dependent Ca2+ influx), was shown to lack (45)Ca2+ entry from outside upon AED stimulation. In contrast, cells grown at 25 degrees C behave like the wildtype. To check the functional properties in more detail, fluorochrome-loaded 35 degrees C cells were stimulated, not only with AED (EC(100) = 10(-6) M in wildtype cells), but also with 4-chloro-meta-cresol, (4CmC, 0.5 mM), a permeable activator of ryanodine receptor-type Ca2+ release channels, usually at extracellular [Ca2+] of 50 microM, and eventually with a Ca2+ chelator added. We confirm that pwA-nd12(35 degrees C) cells lack any Ca2+ influx and any exocytosis of trichocysts in response to any stimulus. As we determined by x-ray microanalysis, total calcium content in alveolar sacs (subplasmalemmal stores) known to be mobilized upon exocytosis stimulation in wild-type cells, contain about the same total calcium in 35 degrees C as in 25 degrees C cells, and Ca2+ mobilization from alveoli by AED or 4CmC is also nearly the same. Due to the absence of any AED-induced Ca2+ influx in 35 degrees C cells and normal Ca2+ release from stores found by x-ray microanalysis one can exclude a "CICR"-type mechanism (Ca2+-induced Ca2+ release) and imply that normally a store-operated Ca2+ ("SOC") influx would occur (as in 25 degrees C cells). Furthermore, 35 degrees C cells display a significantly lower basal intracellular [Ca2+], so that any increase upon stimulation may be less expressed or even remain undetected. Under these conditions, any mobilization of Ca2+ from stores cannot compensate for the lack of Ca2+ influx, particularly since normally both components have to cooperate to achieve full exocytotic response. Also striking is our finding that 35 degrees C cells are unable to perform membrane fusion, as analyzed with the Ca2+ ionophore, A23187. These findings were corroborated by cryofixation and freeze-fracture analysis of trichocyst docking sites after AED or 4CmC stimulation, which also revealed no membrane fusion. In sum, in nd12 cells increased culture temperature entails multiple defects, notably insensitivity to any Ca2+ signal, which, moreover, cannot develop properly due to a lower basal [Ca2+] level and the lack of Ca2+ influx, despite normal store activation.

Animals↗

Stimulation of cytokine release and adhesion molecule expression by products of Viridans streptococci.

The viridans streptococci (VS) are associated with the development of a rapidly fulminant shock syndrome in neutropenic patients. A panel of 52 VS strains isolated from the blood of neutropenic patients was used to demonstrate the ability of culture supernatants and cell walls of VS to induce release of the proinflammatory cytokines tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-8 from whole blood in a dose- and strain-dependent fashion. Intercellular adhesion molecule-1 was shown to be markedly up-regulated on endothelial cells after incubation with plasma from blood exposed to cell walls or culture supernatants. This up-regulation was blocked by IL-1 receptor antagonist but not neutralizing antibody against TNF-alpha. These data may help explain the pathogenesis of the viridans streptococcal shock syndrome in neutropenic patients.

Bacteremia↗