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Biomedical subjects

D G James

Publications and source records attributed to D G James.

At least 19 recordsLinked to original sources

Whipple's disease: a granulomatous masquerader.

Whipple's disease is a multisystemic infection that affects middle-aged white men. It typically presents with fever, polyarthritis, diarrhea, steatorrhea, and weight loss. Many other systems can be involved, however, including the central nervous system, heart, lymphatics, lungs, bone marrow, and skin. Recent work has demonstrated the causative organism to be a complex bacteria, Tropheryma whipplei. The diagnosis is established most securely by periodic acid-Schiff staining of foamy monocyte-macrophages in biopsy tissue and body fluids, by electron microscopy, which reveals bacilli within membrane-bound vesicles, and by molecular amplification techniques using polymerase chain reaction of tissues and body fluids. The differential diagnosis includes chronic multisystemic infections and granulomatous disorders, because Whipple's disease is a fascinating blend of both. The condition can resemble sarcoidosis and mycobacterial disease and fungal, protozoal, and bacillary infections. Earlier diagnosis leads to earlier treatment and hopefully the prevention of chronic disabling complications and needless mortality from this once uniformly fatal condition.

Diagnosis, Differential↗

Identification of a female-specific, antennally active volatile compound of the currant stem girdler.

We identified (Z)-9-octadecen-4-olide as a female-specific, antennally active compound from the currant stem girdler Janus integer Norton. Female specificity was demonstrated by gas chromatographic comparison of liquid chromatography fractions of male and female volatile emissions and whole body extracts. The gamma-lactone was identified by coupled gas chromatographic-electroantennographic detection (GC-EAD), coupled gas chromatographic-mass spectrometric (GC-MS) analysis, microchemical reactions, and GC and MS comparison with authentic standards. GC-EAD analysis of female volatile emissions and cuticular extracts showed a single peak of activity on male antennae, which was not present in male-derived materials. Female antennae did not respond to any of the tested materials. The hydrogenation product of the natural EAD-active material was a known saturated gamma-lactone. The mass spectrum of the dimethyl disulfide derivative of the natural y -lactone was consistent with a double bond present in the 9 position. Comparison of the natural gamma-lactone and a synthesized racemic mixture of (Z)-9-octadecen-4-olide on a chiral GC column showed the presence of a single enantiomer in the natural material.

Animals↗

Stability of benzodiazepines in formaldehyde solutions.

Benzodiazepine-type drugs are used in the treatment of a number of pathologic disorders, but they may be implicated in forensic toxicology cases because of their abuse potential. Occasionally, it becomes necessary to measure drug levels following exposure to formaldehyde (postembalming or after tissue storage) if drug involvement was not previously suspected. Virtually no information exists on the decomposition of benzodiazepines in the presence of formaldehyde (the active ingredient in many embalming fluids), yet formaldehyde is known to be highly reactive, particularly with nitrogen-containing compounds. In order to evaluate the effects of formaldehyde on benzodiazepines, 10 benzodiazepine drugs were exposed to various concentrations of formaldehyde and various pH conditions (to simulate potential postembalming conditions), and the decomposition of each drug was measured by high-performance liquid chromatography over a 30-day period. The decomposition rates of all but one of the benzodiazepines were accelerated (to differing degrees) by formaldehyde as compared to controls, and this decomposition was in several cases both pH and formaldehyde concentration dependent. Thus, forensic examiners must be particularly cautious when attempting to determine benzodiazepine concentrations postembalming because the compound may have reacted with formaldehyde to form other products not inherently obvious analytically. Determination of these reaction products will serve to provide alternate analytes, allowing for establishment of accurate conclusions during forensic analyses.

Anti-Anxiety Agents↗

Sarcoidosis 2001.

In every decade, sarcoidosis makes a chameleon-like change so its profile needs to be updated. It was first recognised as a dermatological curiosity which evolved into a multisystem disorder with bone cysts, uveitis, and intrathoracic involvement. New dimensions were uncovered by biochemistry and immunology, bringing it still nearer the elusive enigma, namely the cause of sarcoidosis. Aetiology includes an understanding of a genetic predisposition and environmental trigger factors. What was left undone in the 20th century will become evident in the 21st century with more sophisticated technology. Likewise, conventional treatments of the past will be superseded by cytokines and other magic bullets of the millennium.

Acute Disease↗

A clinicopathological classification of granulomatous disorders.

Granulomatous disorders comprise a large family sharing the histological denominator of granuloma formation. A granuloma is a focal compact collection of inflammatory cells, mononuclear cells predominating, usually as a result of the persistence of a non-degradable product and of active cell mediated hypersensitivity. There is a complex interplay between invading organism or prolonged antigenaemia, macrophage activity, a Th1 cell response, B cell overactivity and a vast array of biological mediators. Differential diagnosis and management demand a skilful interpretation of clinical findings and pathological evidence. They are classified into infections, vasculitis, immunological aberration, leucocyte oxidase deficiency, hypersensitivity, chemicals, and neoplasia.

B-Lymphocytes↗

Bovine versus rat adrenal chromaffin cells: big differences in BK potassium channel properties.

Both bovine and rat adrenal chromaffin cells have served as pioneering model systems in cellular neurophysiology, including in the study of large conductance calcium- and voltage-dependent K(+) (BK) channels. We now report that while BK channels dominate the outward current profile of both species, specific gating properties vary widely across cell populations, and the distributions of these properties differ dramatically between species. Although BK channels were first described in bovine chromaffin cells, rapidly inactivating ones were discovered in rat chromaffin cells. We report that bovine cells can also exhibit inactivating BK channels with varying properties similar to those in rat cells. However, a much smaller proportion of bovine cells exhibit inactivating BK current, the proportion of the total current that inactivates is usually smaller, and the rate of inactivation is often much slower. Other gating features differ as well; the voltage dependence of channel activation is much more positive for bovine cells, and their rates of activation and deactivation are faster and slower, respectively. Modeling studies suggest that channel heterogeneity is consistent with varying tetrameric combinations of inactivation-competent versus -incompetent subunits. The results suggest that chromaffin BK channel functional nuances represent an important level for evolutionary tailoring of autonomic stress responses.

Adrenal Glands↗

Parotid gland sarcoidosis.

Parotid gland sarcoidosis occurs in 6% of patients with sarcoidosis. It was bilateral in 24 (73%), slightly commoner in women, and presented in the majority in the 20 to 40 year age group. There was widespread involvement of other systems, particularly intrathoracic, peripheral lymph-adenopathy, uveitis, lacrimal gland enlargement and skin disease. Patterns of involvement may be pathognomonic as in Heerfordt's syndrome. This account provides the differential diagnosis, imaging and biopsy techniques, and treatment.

Adult↗

Life-threatening situations in sarcoidosis.

Life-threatening situations in sarcoidosis are extremely rare. They may be due to failure of vital organs--lungs, heart, kidney, liver and brain--and usually due to irreversible fibrosis. Respiratory failure follows irreversible pulmonary fibrosis and the development of cor pulmonale. Cardiac sarcoidosis is more sinister for it may be silent, ill-recognised with sudden death or high morbidity. It needs sophisticated techniques to uncover this latent iceberg. Renal failure may be due to granulomatous interstitial nephritis and/or nephrocalcinosis. Hepatic failure is due to intrahepatic cholestasis, portal hypertension and bleeding oesophageal varices. Neurosarcoidosis carries a mortality of 10 per cent, over twice that of sarcoidosis overall. The treatment of each situation is discussed including organ transplantation.

Adult↗

Descriptive definition and historic aspects of sarcoidosis.

Sarcoidosis is set within the framework of a large family of granulomatous disorders, so it has many mimics. Granuloma formation is defined with its immunologic basis. The criteria of activity of sarcoidosis are included in the broadly based definition. Future knowledge will derive from basic immunology and molecular biology. Historic aspects are based on pioneers, who have died, and their seminal contributions. Evolution of knowledge derives from information gained at international conferences and from our biennial journal, "Sarcoidosis, Vasculitis and Diffuse Lung Diseases."

Congresses as Topic↗

Differential diagnosis of facial nerve palsy.

Facial nerve palsy is the most frequent neurological presentation of sarcoidosis. It occurs with equal frequency on the right or left side, and equally unilateral or bilateral. When bilateral facial palsy develops in a young adult, sarcoidosis is the most likely cause. In our series of 147 patients with ocular sarcoidosis, facial palsy occurred in 12 per cent and parotid gland enlargement in 10 per cent. Resolution of facial palsy is complete in 80 per cent of patients. It does not recur, unlike orofacial granulomatosis in which facial palsy tends to be recurrent. The differential diagnosis is large (Table I) and needs full investigation in order to provide a better understanding of the treatment and prognosis. A 7-point scheme of management is set out for the patient with idiopathic facial nerve palsy.

Adult↗

Granulomatous infections: etiology and classification.

Granulomatous disorders are frequently due to a wide variety of infections. Over the past decade advances in molecular diagnostic techniques have allowed identification of organisms involved in granulomatous disorders that previously were of unknown etiology. On the basis of currently available information, granulomatous infections can now be classified in three categories. Group 1 infections are due to a well-recognized organism. Group 2 comprises infections due to organisms that have been recently identified in granulomas by molecular methods but are not readily isolated by conventional microbiological techniques. Group 3 consists of disorders for which the causal organisms have not yet been identified but are strongly suspected; further advances in diagnostic techniques will lead to reclassification of some of these disorders as group 2. This review describes the etiology, histopathologic features, and classification of granulomatous disorders, with an emphasis on those of groups 2 and 3.

Bacterial Infections↗

A new immunosuppressant: tacrolimus.

Tacrolimus is the new name for the Japanese immunosuppressant drug FK506. It blocks interleukin 2 transcription thereby inhibiting the CD4 Th-1 lymphocyte response to foreign antigens. It also selectively inhibits cytokine secretion of IL3, IL4 and interferon-gamma. It is metabolised by the cytochrome P-450 enzyme system. The results of two trials indicate that it is similar to cyclosporin in efficacy and toxicity.

Graft Rejection↗