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Biomedical subjects

R R Jacobson

Publications and source records attributed to R R Jacobson.

At least 19 recordsLinked to original sources

Copper(I) complexes, copper(I)/O(2) reactivity, and copper(II) complex adducts, with a series of tetradentate tripyridylalkylamine tripodal ligands.

Copper(I) and copper(II) complexes possessing a series of related ligands with pyridyl-containing donors have been investigated. The ligands are tris(2-pyridylmethyl)amine (tmpa), bis[(2-pyridyl)methyl]-2-(2-pyridyl)ethylamine (pmea), bis[2-(2-pyridyl)ethyl]-(2-pyridyl)methylamine (pmap), and tris[2-(2-pyridyl)ethyl]amine (tepa). The crystal structures of the protonated ligand H(tepa)ClO(4), the copper(I) complexes [Cu(pmea)]PF(6) (1b-PF(6)), [Cu(pmap)]PF(6) (1c-PF(6)), and copper(II) complexes [Cu(pmea)Cl]ClO(4).H(2)O (2b-ClO(4).H(2)O), [Cu(pmap)Cl]ClO(4).H(2)O (2c-ClO(4).H(2)O), [Cu(pmap)Cl]ClO(4) (2c-ClO(4)), and [Cu(pmea)F](2)(PF(6))(2) (3b-PF(6)) were determined. Crystal data: H(tepa)ClO(4), formula C(21)H(25)ClN(4)O(4), triclinic space group P1, Z = 2, a = 10.386(2) A, b = 10.723(2) A, c = 11.663(2) A, alpha = 108.77(3) degrees, beta = 113.81(3) degrees, gamma = 90.39(3) degrees; 1b-PF(6), formula C(19)H(20)CuF(6)N(4)P, orthorhombic space group Pbca, Z = 8, a = 14.413(3) A, b = 16.043(3) A, c = 18.288(4) A, alpha = beta = gamma = 90 degrees; (1c-PF(6)), formula C(20)H(22)CuF(6)N(4)P, orthorhombic space group Pbca, Z = 8, a = 13.306(3) A, b = 16.936(3) A, c = 19.163(4) A, alpha = beta = gamma = 90 degrees; 2b-ClO(4).H(2)O, formula C(19)H(22)Cl(2)CuN(4)O(5), triclinic space group P1, Z = 4, a = 11.967(2) A, b = 12.445(3) A, c = 15.668(3) A, alpha = 84.65(3) degrees, beta = 68.57(3) degrees, gamma = 87.33(3) degrees; 2c-ClO(4).H(2)O, formula C(20)H(24)Cl(2)CuN(4)O(5), monoclinic space group P2(1)/c, Z = 4, a = 11.2927(5) A, b = 13.2389(4) A, c = 15.0939(8) A, alpha = gamma = 90 degrees, beta = 97.397(2) degrees; 2c-ClO(4), formula C(20)H(22)Cl(2)CuN(4)O(4), monoclinic space group P2(1)/c, Z = 4, a = 8.7682(4) A, b = 18.4968(10) A, c = 13.2575(8) A, alpha = gamma = 90 degrees, beta = 94.219(4) degrees; 3b-PF(6), formula [C(19)H(20)CuF(7)N(4)P](2), monoclinic space group P2(1)/n, Z = 2, a = 11.620(5) A, b = 12.752(5) A, c = 15.424(6) A, alpha = gamma = 90 degrees, beta = 109.56(3) degrees. The oxidation of the copper(I) complexes with dioxygen was studied. [Cu(tmpa)(CH(3)CN)](+) (1a) reacts with dioxygen to form a dinuclear peroxo complex that is stable at low temperatures. In contrast, only a very labile peroxo complex was observed spectroscopically when 1b was reacted with dioxygen at low temperatures using stopped-flow kinetic techniques. No dioxygen adduct was detected spectroscopically during the oxidation of 1c, and 1d was found to be unreactive toward dioxygen. Reaction of dioxygen with 1a-PF(6), 1b-PF(6), and 1c-PF(6) at ambient temperatures leads to fluoride-bridged dinuclear copper(II) complexes as products. All copper(II) complexes were characterized by UV-vis, EPR, and electrochemical measurements. The results manifest the dramatic effects of ligand variations and particularly chelate ring size on structure and reactivity.

Chelating Agents↗

Leprosy.

Leprosy is an ancient disease which is still poorly understood and often feared by the general public and even by some healthcare professionals. Fortunately, improvements in the management of leprosy over the past three decades have diminished the stigma and greatly altered the outlook for patients. Public understanding of the disease has benefited from WHO's goal of eliminating leprosy as a public health problem by the year 2000. Unfortunately that goal has also led many to believe that leprosy has been or will soon be eradicated. This will not happen in the near future because, despite a fall in registered cases, the incidence of the disease has changed very little, and eradication of a bacterial infectious disease such as this is unlikely with chemotherapy alone. Nevertheless, as a result of the WHO's efforts, patients nearly everywhere should have access to care, and the incidence may begin to diminish if adequate control efforts are maintained beyond the year 2000. Given the mobility of patients today a physician anywhere may occasionally see a case or be asked about the disease so a basic understanding of leprosy and its management should prove useful.

Drug Administration Schedule↗

Enhanced displacement of [3H]imipramine, but not [3H]paroxetine binding by plasma from depressed patients.

Plasma from healthy subjects inhibited the binding of [3H]imipramine competitively and [3H]paroxetine non-competitively to platelet membranes in a volume-dependent manner. Plasma from 40 depressed patients was more effective at inhibiting [3H]imipramine, but not [3H]paroxetine, binding compared to plasma from matched controls. This difference was not related to recent antidepressant treatment. The results suggest that the concentration of an endogenous modulator of [3H]imipramine binding is increased in depressive illness. The concentration of alpha 1-acid glycoprotein, a proposed endogenous modulator of [3H]imipramine binding, did not differ between depressed patients and controls. Our results suggest that factors other than alpha 1-acid glycoprotein may modulate [3H]imipramine binding.

Adult↗

Neuropsychology of thallium poisoning.

Cases of thallium poisoning are rare and neuropsychological assessment has only been reported in detail in one other case. In the case reported here, neuropsychological assessments were carried out three, 12, and 54 months after diagnosis of thallium poisoning in a man who had acutely shown a number of neurological signs including confusion and disorientation and generalised slowing of EEG which was more prominent on the left. Evidence suggested that he had been exposed to thallium over a period of weeks. Neuropsychological assessment indicated an unexpected weakness in verbal abilities which persisted. This finding is consistent with the only other published case report which details neuropsychological effects after a single large dose of thallium and which also found a lateralised impairment.

Adult↗

Seasonal cyclothymia to seasonal bipolar affective disorder: a double switch after stroke.

The appearance of bipolar affective disorder after stroke depends on the presence of two factors: a predisposing factor of either genetic loading or subcortical atrophy, and a lesion of specific corticolimbic pathways involving the right hemisphere. Whether cyclothymia and seasonal affective disorder further predispose to poststroke affective disorder is not clear. A case is described which highlights these issues. The aetiological factors, pathophysiology, and diagnosis are discussed.

Aged↗

Needed research in chemotherapy of leprosy related to the individual patient.

The chemotherapy of leprosy was rendered markedly more effective by the introduction of WHO/MDT in 1981. The prospects for further improvements, both by shortening duration and by developing fully supervisable intermittent regimens, appear good at this time. These developments should aid the efforts to attain the goal of elimination of leprosy as a public health problem. For the foreseeable future, however, the goal of eradication of leprosy will continue to elude us.

Drug Therapy, Combination↗

The post-concussional syndrome: physiogenesis, psychogenesis and malingering. An integrative model.

Current models of post-concussional symptoms after mild head injury rest on the dichotomy between organic and psychogenic factors, which underpins Lishman's formulation; organic genesis and psychologically-driven persistence (Br J Psychiatry 1988; 153: 460-469). Recent prospective neuropsychological and bio-social studies of mild head injury, and perspectives from cognitive behavioural and health psychology, are reviewed. It is argued that the organic-psychogenic conceptualization inadequately explains chronic post-concussional symptoms. Psychosocial and cognitive-behavioural factors and the coping process may influence post-concussional symptoms over their entire time course, in particular the late phase. A multifactorial model of chronic post-concussional symptoms is proposed which integrates biological processes with these factors. It is through the recognition and identification of separate processes that questions about outcome, the limits of the impact of organic and psychosocial factors, the nature of exaggeration, and appropriate therapy, may be resolved.

Adaptation, Psychological↗

Lack of cognitive recovery following withdrawal from long-term benzodiazepine use.

Twenty-one patients with significant long-term therapeutic benzodiazepine (BZ) use, who remained abstinent at 6 months follow-up after successfully completing a standardized inpatient BZ withdrawal regime, and 21 normal controls matched for age and IQ but not for anxiety, were repeatedly tested on a simple battery of routine psychometric tests of cognitive function, pre- and post-withdrawal and at 6 months follow-up. The results demonstrated significant impairment in patients in verbal learning and memory, psychomotor, visuo-motor and visuo-conceptual abilities, compared with controls, at all three time points. Despite practice effects, no evidence of immediate recovery of cognitive function following BZ withdrawal was found. Modest recovery of certain deficits emerged at 6 months follow-up in the BZ group, but this remained significantly below the equivalent control performance. The implications of persisting cognitive deficits after withdrawal from long-term BZ use are discussed.

Adult↗

Platelet 5-HT uptake sites in depression: three concurrent measures using [3H] imipramine and [3H] paroxetine.

Platelet 5-HT uptake sites were measured in 40 depressed patients and 40 controls using [3H] imipramine binding, defined with desmethylimipramine (DMI) and Na+ dependence, and [3H] paroxetine binding. In control subjects the Bmax of DMI defined [3H] imipramine binding was significantly higher than both Na+ dependent [3H] imipramine (by 30%) and [3H] paroxetine binding (by 22%). The Bmax of Na+ dependent [3H] imipramine and [3H] paroxetine binding did not differ significantly. The Kd of Na+ dependent [3H] imipramine binding was significantly lower than the Kd of DMI defined [3H] imipramine binding. The binding of DMI defined and Na+ dependent [3H] imipramine and [3H] paroxetine did not differ significantly between depressed patients and controls in the total group, in those depressed patients and controls in the total group, in those depressed patients who had never taken antidepressants or in those depressed patients who had been recently withdrawn from antidepressants. This study provides no support for the view that the number of platelet 5-HT uptake sites are reduced in depression.

Adult↗

Fourteen cases of imposed upper airway obstruction.

Imposed upper airway obstruction was diagnosed as the cause of recurrent and severe cyanotic episodes in 14 patients. Episodes started between 0.8 and 33 months of age (median 1.4) and occurred over a period of 0.8 to 20 months (median 3.5). Diagnosis was made by covert video surveillance, instituted after either (a) the observation that episodes began only in the presence of one person, or (b) characteristic findings on physiological recordings, lasting between 12 hours and three weeks, performed in hospital or at home. Surveillance was undertaken for between 15 minutes and 12 days (median 24 hours) and resulted in safety for the patient and psychiatric assessment of the parent: mother (n = 12), father (n = 1), and grandmother (n = 1). These revealed histories of sexual, physical, or emotional abuse (n = 11), self harm (n = 9), factitious illness (n = 7), eating disorder (n = 10), and previous involvement with a psychiatrist (n = 7). Management of the abusing parents is complex, but recognition of their psychosocial characteristics may allow earlier diagnosis. Imposed upper airway obstruction should be considered and excluded by physiological recordings in any infant or young child with recurrent cyanotic episodes. If physiological recordings fail to substantiate a natural cause for episodes, covert video surveillance may be essential to protect the child from further injury or death.

Airway Obstruction↗

The activity of rifabutin against Mycobacterium leprae.

Minimal effective doses of rifabutin and rifampicin were determined in Mycobacterium leprae isolated from skin biopsies of newly diagnosed, previously untreated lepromatous leprosy patients. Rifabutin was more potent than rifampicin. Our previous report that rifabutin was fully active against rifampicin-resistant M. leprae could not be confirmed. Examination of two strains of rifampicin-resistant M. leprae from elsewhere, and a repeat experiment on our original strain of rifampicin-resistant bacilli, showed full cross-resistance between rifampicin and rifabutin. A clinical trial in three newly diagnosed, previously untreated lepromatous patients showed that rifabutin has rapid bactericidal activity.

Adult↗

Skin pigmentation from clofazimine therapy in leprosy patients: a reappraisal.

Skin biopsy specimens from two lepromatous leprosy patients with dark brown pigmentation who were receiving long-term clofazimine therapy were studied. Ceroid-lipofuscin pigment was demonstrated inside macrophages that contained numerous phagolysosomes. These contained lipids and clofazimine that appeared as electron-lucent vacuoles and a lipofuscin pigment that was electron dense, granular, and lamellated. Although the presence of the drug in tissues contributed to the skin pigmentation, the main cause was a drug-induced, reversible ceroid lipofuscinosis.

Aged↗

Cortical and diencephalic lesions in Korsakoff's syndrome: a clinical and CT scan study.

Twenty-five male alcoholic Korsakoff patients were compared with age and sex-matched non-Korsakoff chronic alcoholics and healthy volunteers on clinical and CT brain scan parameters. The scans were assessed by planimetry, visual grading procedures and computerized analysis. Reliable measures of third ventricular size were developed. The Korsakoff patients had wider third ventricles, larger lateral ventricles and wider interhemispheric fissures than the comparison groups; but sulcal and Sylvian fissure widths were equivalent in Korsakoff and non-Korsakoff alcoholics. The results suggest that, in addition to their well-established diencephalic lesions, many Korsakoff patients have sustained widespread cerebral damage. Shrinkage in the frontal brain regions appears to be especially pronounced. The implications for a dual aetiology of alcoholic Korsakoff's syndrome involving thiamine deficiency and features associated with alcoholism, probably direct alcohol neurotoxicity, are discussed.

Alcohol Amnestic Disorder↗

Patterns of neuropsychological deficit in alcoholic Korsakoff's syndrome.

Twenty-five male and 13 female patients with alcoholic Korsakoff's syndrome (AKS) were compared with age- and sex-matched non-Korsakoff chronic alcoholics and healthy volunteers in a neuropsychological study, which included computer-administered tests of cognitive function. The performance of male Korsakoff patients was significantly inferior to that of healthy male controls, not only in tests of memory, but also in visuo-perceptual tasks with a speed or motor component, and on category sorting and verbal fluency measures. Compared with male alcoholics, the performance of male Korsakoff patients was again inferior on similar tests. Female Korsakoff patients showed more extensive deficits compared with female controls, but differed less from matched female alcoholics. The results suggest that, in addition to their amnesia, many Korsakoff patients have sustained widespread cognitive deficits, affecting particularly visuo-perceptual and abstracting functions, which are sensitive to cortical lesions. The range of deficits falls short of what may be regarded as 'global' in male, but probably not in female, Korsakoffs. The implications for a dual aetiology of AKS involving thiamine deficiency and other features associated with alcoholism, probably direct alcohol neurotoxicity, are discussed.

Adult↗