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Biomedical subjects

J B Chalk

Publications and source records attributed to J B Chalk.

30 records · Page 2Linked to original sources

Sensorimotor peripheral neuropathy in rheumatoid arthritis.

We describe 3 patients with severe sensorimotor neuropathy complicating rheumatoid arthritis. Two patients had evidence of vasculitis and an axonal neuropathy. These patients were unusual in that the neuropathy occurred early in the course of rheumatoid arthritis. The third patient had a demyelinating neuropathy with a high cerebrospinal fluid protein level, and is a probable example of a chronic inflammatory neuropathy occurring in rheumatoid arthritis. All patients improved or were stabilized with corticosteroid therapy.

Aged↗

Improvement in chronic hepatocerebral degeneration following liver transplantation.

Chronic progressive hepatocerebral degeneration with spastic paraparesis, dementia, dysarthria, ataxia, tremor, and neuropsychiatric symptoms follows long-standing portal-systemic shunting, is associated with structural changes in the central nervous system, and does not respond to conventional therapy for hepatic encephalopathy. A case of advanced chronic liver disease with severe, progressive hepatocerebral degeneration after 23 yr of portal-systemic shunting is reported in whom there was significant objective improvement in intellectual function and in the chronic neurological signs 3 mo after orthotopic liver transplantation and further improvement 12 mo after transplantation.

Adult↗

Familial occurrence of multiple sclerosis with thyroid disease and systemic lupus erythematosus.

Multiple sclerosis (MS) has some features which suggest it is an autoimmune disease. Autoimmune diseases frequently occur in families, and patients and families often have more than one type of autoimmune disease. However, there are few reports of MS occurring in patients or families with other autoimmune conditions. It is difficult to make a separate diagnosis of MS in a patient who has a systemic autoimmune disease such as systemic lupus erythematosus (SLE) or Sjögren's syndrome, because these diseases can affect the nervous system directly. However, it is possible to make independent diagnoses of MS and an autoimmune disease confined to another single organ in the same patient, or diagnoses of MS and SLE (or other autoimmune diseases) in different family members. Here we describe clinically definite MS in 2 sisters, one of whom had Graves' disease, and the other of whom had a daughter with SLE and with a high titre of anti-thyroid antibodies. Other female family members over 4 generations had histories of thyroid disease, MS and Addison's disease. Available family members were HLA typed. The MS patients were positive for HLA DR2. All but one of the affected family members were related to the proband on the maternal side, and all of these affected females shared an HLA haplotype. However, this haplotype was also present in unaffected individuals. Thus HLA type alone cannot account for the familial occurrence of these disorders. We conclude that, in this family, MS, like autoimmune thyroid disease and SLE, may be an autoimmune disease developing in genetically predisposed individuals.

Adult↗

An intracranial arteriovenous malformation and palatal myoclonus related to pseudoxanthoma elasticum.

Pseudoxanthoma elasticum is a rare hereditary disorder of elastic tissue with central nervous system manifestations due to occlusive vascular disease and aneurysm formation. Here we report the first recorded case of an intracranial arteriovenous malformation (AVM) in a patient with pseudoxanthoma elasticum. The AVM, which was located in the pons, also had an unusual manifestation, namely palatal myoclonus.

Adult↗

Connective tissue disease mimicking multiple sclerosis.

Systemic lupus erythematosus, primary Sjögren's syndrome and systemic sclerosis may be associated with acute transverse myelitis and chronic relapsing neurological syndromes mimicking multiple sclerosis in the same individuals and/or their relatives. We now present three cases which suggest that there is a wide spectrum of connective tissue disorders mimicking multiple sclerosis and acute disseminated encephalomyelitis. These cases demonstrate that the diagnosis of multiple sclerosis should be kept under constant review by searching for the development of connective tissue disorders in the patients or their relatives.

Adult↗

Progressive encephalomyelitis with rigidity: a case report with magnetic resonance imaging findings.

A 52 year old woman presented with pain in the back and upper limbs and progressive weakness and sensory impairment of the upper and lower limbs. She developed frequent episodes of severe generalised muscle spasms associated with piloerection and hyperventilation. Nerve conduction studies and electromyography were normal. MRI demonstrated a lesion of the cervical spinal cord and lower brainstem. A biopsy of the cord revealed perivascular cuffing with mononuclear cells and inflammatory changes in the parenchyma, with increased numbers of microglia, reactive astrocytes and plasma cells. Following treatment with corticosteroids she showed substantial improvement.

Brain Stem↗

Correlations between in vitro dissolution, in vivo bioavailability and hypoglycaemic effect of oral glibenclamide.

A study has been carried out investigating four different marketed oral preparations of glibenclamide, correlating the effectiveness of the drug in these preparations in lowering plasma glucose concentrations with the in vitro dissolution of the drug, measured by the British Pharmacopoeal and Desaga methods, and the in vivo bioavailability, assessed in 12 healthy human volunteers. The two dissolution methods yielded different rank orders of ease of dissolution of the drug from the various preparations; the findings of neither dissolution method correlated adequately with the results of the in vivo bioavailability studies, which correctly predicted the abilities of the preparations to reduce plasma glucose concentrations. Relative to an oral glibenclamide solution the bioavailabilities of the drug from three tablet preparations were 0.69, 0.49 and 0.24. The mean elimination half-life of the drug was 1.5 h and assuming complete bioavailability of the drug from oral solution the mean systemic clearance was 0.095 l kg-1h-1, and the mean apparent volume of distribution was 0.20 l kg-1. It is concluded that it may be unsafe to use in vitro dissolution data as a basis for assessing the bioequivalences of different glibenclamide preparations intended for oral use.

Adult↗

Cortisol production during high dose dexamethasone therapy in neurological and neurosurgical patients.

Simultaneous plasma dexamethasone and cortisol levels were followed at intervals over 8 hour periods on 40 occasions in 19 subjects who received regular high dosage dexamethasone therapy (rarely less than 12 mg a day) for various neurological and neurosurgical conditions. Lower dexamethasone doses (for example 2 mg daily for 2 days) normally suppress adrenal cortical production of cortisol to below 50 micrograms/l for at least 8 hours. However, in 12 of the 35 studies that did not take place at the first steroid dose or in subjects taking second daily bolus steroid dosage such suppression was not present 8 to 12 hours after dexamethasone intake, though it was shown that dexamethasone could suppress cortisol production in all these cases. Failure of maintained suppression despite the high steroid dose appeared to be related to rapid elimination of dexamethasone. These findings may help explain the relative rarity of adrenal failure in clinical neurological practice after high dosage steroid therapy is ceased.

Adult↗

Phenytoin impairs the bioavailability of dexamethasone in neurological and neurosurgical patients.

Plasma concentration-time data after oral and intravenous administration of dexamethasone have been subjected to pharmacokinetic analysis in six neurological or neurosurgical patients taking the steroid with phenytoin, and in nine patients (one studied twice) taking dexamethasone without phenytoin. An additional patient was studied before and during phenytoin intake. Apparent volume of distribution was similar in the two groups, but the group treated with phenytoin had an almost statistically significantly shorter dexamethasone mean terminal half-life, an approximately trebled mean plasma clearance, and a mean oral bioavailability of the steroid of only 33%, compared with a mean 84% oral bioavailability in those not receiving phenytoin. To achieve a given plasma dexamethasone concentration, patients treated with the steroid and phenytoin may need oral dexamethasone doses several times those required by patients not receiving phenytoin.

Adult↗

Bioavailability and pharmacokinetics of phenytoin during pregnancy.

Five epileptic women needing to commence phenytoin therapy during pregnancy received a single intravenous and a single oral dose of phenytoin several days apart before starting regular intake of the drug. Plasma phenytoin concentration - time data were analysed by three different pharmacokinetic techniques. However assessed, the mean oral bioavailability of the drug proved to be about 90% of the intravenous bioavailability. This finding makes it unlikely that impaired bioavailability accounts for the increase in oral phenytoin dosage necessary in pregnancy to maintain plasma phenytoin concentrations at pre-pregnancy values. Phenytoin clearance in the pregnant subjects was approximately double the published values for phenytoin clearance in non-pregnant persons. This suggests that increased (metabolic) clearance accounts for the increased phenytoin dosage requirement of pregnancy.

Aging↗

A reproducible method for automated extraction of brain volumes from 3D human head MR images.

An automated method for extracting brain volumes from three commonly acquired three-dimensional (3D) MR images (proton density, T1 weighted, and T2-weighted) of the human head is described. The procedure is divided into four levels: preprocessing, segmentation, scalp removal, and postprocessing. A user-provided reference point is the sole operator-dependent input required. The method's parameters were first optimized and then fixed and applied to 30 repeat data sets from 15 normal older adult subjects to investigate its reproducibility. Percent differences between total brain volumes (TBVs) for the subjects' repeated data sets ranged from .5% to 2.2%. We conclude that the method is both robust and reproducible and has the potential for wide application.

Aged↗

Rearrangement of valproate glucuronide in a patient with drug-associated hepatobiliary and renal dysfunction.

Formation of beta-glucuronidase-resistant "glucuronides" of valproic acid (VPA) by intramolecular rearrangement of biosynthetic valproate glucuronide in vivo was investigated in a patient diagnosed with VPA-associated hepatobiliary and renal dysfunction. Plasma elimination half-life of VPA following cessation of the drug was 13.9 h. At the time of the toxicity, the concentration of conjugated VPA in plasma was very high (36-54% of nonconjugated VPA levels) relative to that in normal patients (2.9%). The fraction of conjugated VPA resistant to beta-glucuronidase hydrolysis was 0.28-0.47 in plasma and 0.15-0.42 in urine. The corresponding fraction in urine from normal patients receiving VPA therapy was 0.044. The evidence was consistent with retarded elimination of biosynthetic VPA glucuronide caused by renal and hepatobiliary dysfunction. Consequent prolongation of circulation of VPA glucuronide at the slightly alkaline pH of blood would permit extensive intramolecular rearrangement which is known to be pH-, temperature-, and time-dependent. The biological consequences of the presence of such beta-glucuronidase-resistant conjugated VPA in vivo are largely unknown.

Adolescent↗