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Biomedical subjects

A Hoffman

Publications and source records attributed to A Hoffman.

At least 145 records · Page 8Linked to original sources
PubMed1993

Control of cerebral oedema by total hepatectomy and extracorporeal liver support in fulminant hepatic failure.

Keeping a patient with fulminant hepatic failure (FHF) alive until a donor liver is available for transplantation can be a problem. We describe an 18-year-old woman with paracetamol-induced FHF, who was treated by total hepatectomy, hypothermia, plasma exchange, and extracorporeal liver support. The patient was anhepatic for 14 h. The liver-support system consisted of plasma separation and perfusion through a charcoal filter and a hollow-fibre module seeded with matrix-attached porcine hepatocytes. With artificial liver treatment there was reversal of severe neurological dysfunction, normalisation of intracranial pressure, and decreased serum ammonia. The patient underwent emergency transplantation with an ABO-incompatible liver, followed by transplantation with a compatible organ eight days later. The patient has fully recovered and is neurologically intact.

Adolescent↗
PubMed1993

Myocarditis following envenoming with Vipera palaestinae in two horses.

Cardiac disease developed several days to weeks after resolution of local inflammation caused by envenoming by Vipera palaestinae in two horses. In one horse (case A), referred to the hospital for recurrent abdominal pain 8 days after envenoming, a tachyarrhythmia was detected; ventricular premature depolarizations were diagnosed by ECG. A second horse (case B) was found dead without premonitory signs 60 days after envenoming. In both horses, there was extensive necrosis of cardiac ventricular tissues.

Animals↗
PubMed1993

Effect of pretreatment with anticonvulsants on theophylline-induced seizures in the rat.

Seizures, often with fatal outcome, are a manifestation of pronounced theophylline toxicity. Prodromal symptoms are not always apparent, and the seizures are reported to be, in certain cases, refractory to treatment with anticonvulsant drugs. The purpose of this investigation was to examine, by an established animal model, which of the commonly used anticonvulsants can reduce the central nervous system sensitivity to theophylline neurotoxicity and what should be the preferred treatment in cases in which theophylline toxicity is anticipated. The anticonvulsant agents in doses that are found to be effective in other types of experimentally induced seizures in rats, clonazepam 5 mg/kg, diazepam 5 mg/kg, phenytoin 8 mg/kg, phenobarbital 100 mg/kg, valproic acid 150 mg/kg, and magnesium sulphate 300 mg/kg, or the vehicle (controls) were administered intravenously to Lewis female rats. Thirty minutes later, theophylline was infused at a constant rate of 1.3 mg/min until onset of maximal seizures. Theophylline concentrations in the cerebrospinal fluid, brain, and serum were assayed by a high-performance liquid chromatography method. It was found that pretreatment with either clonazepam, diazepam, phenobarbital, or valproic acid increased the central nervous system thresholds to the theophylline-induced seizures, whereas phenytoin and magnesium sulphate did not attenuate the sensitivity of the brain to the stimulatory action of this widely used bronchodilator. Therefore, whenever theophylline toxicity is suspected, treatment with either diazepam, clonazepam, phenobarbital, or valproic acid can reduce the hazard associated with theophylline-induced seizures.

Animals↗
PubMed1993

Lower limb ischaemia in primary antiphospholipid syndrome.

Primary antiphospholipid syndrome (PAPS) is an autoimmune disorder manifested by recurrent thrombosis in the venous and arterial system. We report a group of seven patients with lower limb ischaemia associated with PAPS. Four were male patients and three were females, with a mean age of 37 years. All had a previous deep vein thrombosis and the majority, five out of seven, had a prior cerebrovascular accident (CVA). Prolonged activated thromboplastin time was demonstrated in all our patients and PAPS was established by positive thromboplastin titration index, circulating anticoagulant index and increased anticardiolipin levels. Symptoms included claudication in three, rest pain in four and gangrene in five patients. Angiography demonstrated thrombosis of various segments of the arterial tree including: aorta, iliac, femoral and popliteal arteries. Two patients were treated conservatively and one by percutaneous transluminal angioplasty (PTA) of the distal aorta. A total of eleven vascular surgical procedures were performed in four patients resulting in early postoperative thrombosis (2h-30 days) in 10 cases. Only one graft remained patent, when full heparinisation (1000 units/h) was used perioperatively. We conclude that PAPS patients are at high risk for graft thrombosis and should only be operated upon on full anticoagulation, starting at operation and proceeding indefinitely.

Adolescent↗
PubMed1993

A new route of drug administration: intrauterine delivery of insulin and calcitonin.

High molecular weight drugs in general, and peptides in particular, are usually delivered by parenteral route because they are poorly absorbed or degraded in the gastrointestinal tract. To optimize therapy, it is desirable to search for nonparenteral routes of administration and to deliver the drug in a controlled-release fashion. We report here on the absorption and the systemic biological effect of two peptides, insulin and calcitonin, after instillation into the uterus of the rat. Intrauterine delivery was compared to subcutaneous injections in intact and ovariectomized rats. In addition, we describe results of a preliminary study on calcitonin absorption from controlled-release matrices inserted in the rat uterus. The amount and duration of the hypoglycemic and the hypocalcemic effects induced by intrauterine delivery of insulin and calcitonin, respectively, were equivalent to those obtained after subcutaneous injections. The results were similar in intact and ovariectomized rats. It is concluded that the intrauterine administration of both insulin and calcitonin is bioequivalent to subcutaneous injection. The therapy of a number of clinically important diseases could benefit from this discovery.

Absorption↗
PubMed1993

Role of CRH in glucopenia-induced adrenomedullary activation in rats.

Acute glucoprivation profoundly stimulated hypothalamic-pituitary-adrenocortical (HPA) and adrenomedullary outflows. Whether these responses reflect a single central mechanism regulated by corticotropin-releasing hormone (CRH) has been unclear. This study examined the role of endogenous CRH in HPA and adrenomedullary responses to hypoglycemia in Sprague-Dawley rats, by using anti-CRH immune serum or a CRH antagonist (alpha-helical h/r CRH9-41, and in Lewis rats, a strain characterized by deficient hypothalamic CRH responses during stress. In conscious Sprague-Dawley rats with indwelling arterial and venous cannulas, insulin (0.3 U/kg was injected iv, and responses of serum glucose concentrations and plasma levels of corticotropin (ACTH) and catechols (including epinephrine, EPI; norepinephrine, NE; dihydroxyphenylalanine, DOPA; dihydroxyphenylglycol, DHPG; and dihydroxyphenylacetic acid, DOPAC) were assessed, with or without pretreatment with anti-CRH immune serum (0.5 or 1.0 ml iv or 10 microl icv) or alpha-helical h/r CRH9-41 (130 nmol iv or 13 nmol icv). Responses to insulin (1.0 U/kg iv) were also measured in conscious juvenile Lewis and Fischer 344/N rats. Insulin-induced hypoglycemia markedly increased plasma levels of EPI and ACTH in all groups. Pretreatment iv with 1/0 ml of anti-CRH immune serum blocked the ACTH response to insulin but failed to attenuate the EPI response. alpha-helical h/r CRH9-41, whether given iv or icv, failed to alter ACTH or EPI responses to insulin, although the antagonist did block EPI responses to icv CRH. Hypoglycemia elicited similar increments in ACTH levels in Lewis rats and Fischer 344/N control rats; and although Lewis rats had lower baseline EPI and smaller responses of NE, DHPG, DOPA, and DOPAC levels, the groups did not differ in proportionate increments in EPI levels. The results indicate that the ACTH response to hypoglycemia depends on availability of CRH outside the blood-brain barrier--presumably in the pituitary gland. The findings with icv alpha-helical h/r CRH9-41 can be explained by failure of the antagonist to reach effective concentrations at central sites of action of endogenous CRH, or by mechanisms other than CRH release determining the adrenomedullary response to hypoglycemia. Lewis rats seem to have less adrenomedullary secretion at baseline and smaller responses of NE synthesis and release during hypoglycemia than do Fischer 344/N rats. Neurochemical evidence for differential adrenomedullary and sympathoneural responses during hypoglycemia in all three rat strains is inconsistent with Cannon's view of a functionally unitary sympathoadrenal system. Lewis rats have deficient CRH responses to some stressors but not to others, or else pituitary-adrenomedullary responses in this setting depend on mechanisms other than CRH release in the brain. Both explanations are inconsistent with the doctrine of non-specificity, the main tenet of Selye's stress theory.

Adrenal Medulla↗
PubMed1993

Effect of acute experimental liver dysfunction on the pharmacodynamics of heptabarbital in rats.

The present study aimed to investigate whether the pharmacodynamics of a lipophilic barbiturate, heptabarbital, is altered by liver dysfunction. Heptabarbital was slowly infused i.v., to rats with liver necrosis induced by carbon-tetrachloride, until the rats lost their righting reflex. The concentrations of the drug in serum, brain and CSF were determined in both the diseased animals and solvent-treated controls. Although the concentrations of heptabarbital in the CSF, serum and brain were not significantly different between controls and diseased rats, the total heptabarbital dose required to induce sleep was markedly lower in the diseased animals. Accordingly, the pharmacodynamics of heptabarbital is unaffected in experimental liver dysfunction in rats.

Acute Disease↗
PubMed1993

Regulation of renal glomerular and papillary ANP receptors in rats with experimental heart failure.

Rats with aortocaval (A-V) fistula, an experimental model of congestive heart failure (CHF), display high circulating atrial natriuretic peptide (ANP) levels and a markedly blunted natriuretic response to ANP infusion. The present study was designed to evaluate whether alterations in renal ANP receptors may contribute to renal hyporesponsiveness to ANP in experimental CHF. Densities (Bmax) and dissociation constants (Kd) of both the biologically active (ANPA) and clearance receptors (ANPC) were evaluated in glomerular and papillary membranes from A-V fistula rats (n = 18) and sham-operated controls (n = 20). ANPA and ANPC receptor subtypes were assayed by displacement of 125I-ANP-(99-126) bound to glomerular or papillary membranes by increasing concentrations of unlabeled ANP-(99-126) or des-(18-22)-ANP-(4-23), an analogue which binds only to ANPC. Seven days after the operation, rats with A-V fistula displayed avid sodium retention, elevated plasma renin activity, and approximately a 10-fold increase in plasma ANP levels. Bmax of total ANP binding sites was significantly decreased in rats with A-V fistula compared with controls (220 +/- 61 vs. 399 +/- 88 fmol/mg protein, P < 0.05). The decrease was mainly due to a reduction in ANPA receptor density (51 +/- 10 vs. 110 +/- 15 fmol/mg protein, P < 0.05) with no change in receptor affinity. Likewise, a significant reduction in the density of ANPA (23 +/- 5 vs. 64 +/- 10 fmol/mg protein, P < 0.05) with no change in receptor affinity was observed in papillary membranes of rats with A-V fistula.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Dose-response effect of intrathecal alfentanil on canine lower urinary tract dynamics.

The effect of intrathecal (IT) administration of three different doses (1, 2.5, and 5 micrograms/kg) of alfentanil on lower urinary tract dynamics was examined by urodynamic studies, cystometrograms (CMG), and urethral pressure profiles (UPP) in seven anesthetized dogs. Simultaneous serum drug concentrations were determined by specific radioimmunoassay for time-response analysis. A significant dose-dependent relaxation of urethral musculature expressed by a reduction in UPP values of 41.5% and 38.4% (P < 0.03) was noted 30 min after 5 and 2.5 micrograms/kg IT alfentanil, respectively, whereas the decrease of 13.4-22% in mean CMG values was not significant. All changes in UPP and CMG returned to baseline values by 60 min. The pharmacokinetics of alfentanil from the cerebrospinal fluid to the systemic circulation were linear, i.e., dose-independent with maximal serum concentrations of 0.6, 1.4, and 3.5 ng/mL 10 min after the three respective IT doses. The low serum alfentanil concentrations and the lack of time correlation between the peak values and the changes in urinary tract activity, point to a spinally mediated mechanism. The short-lived effect of IT alfentanil on lower urinary tract dynamics and the relaxation of the bladder neck allow for unobstructed micturition pathways and may avoid urinary retention.

Alfentanil↗
PubMed1993

Kinetics of drug action in disease states. XLI. Effect of adrenalectomy on the hypnotic activity of phenobarbital, the neurotoxicity of theophylline and pain sensitivity in rats.

The purpose of this investigation was to determine the effects of adrenalectomy and adrenalectomy with corticosterone replacement on pain sensitivity and on the pharmacodynamics of a central nervous system depressant, phenobarbital, and a central nervous system stimulant, theophylline. Male Sprague-Dawley rats, bilaterally adrenalectomized, were maintained on normal saline solution or normal saline solution with corticosterone, 160 micrograms/ml, as drinking water for 9 or 11 days. Sham-operated animals served as normal controls. They were then tested for pain sensitivity by the tail-flick method. Phenobarbital or theophylline was infused i.v. slowly until the onset of loss of righting reflex or of maximal seizures, respectively. Samples of cerebrospinal fluid (CSF), blood (for serum) and the brain were obtained at that time and assayed for phenobarbital or theophylline by high-performance liquid chromatography. Compared to the controls, the adrenalectomized rats required a smaller dose and lower concentrations of phenobarbital in serum, brain and CSF (12% decrease) to produce loss of righting reflex. The opposite effect was observed in adrenalectomized rats supplemented with corticosterone. Adrenalectomy had no apparent effect on the dose and the serum, brain and CSF concentrations of theophylline at the onset of maximal seizures whereas adrenalectomized, corticosterone-supplemented animals required a larger dose and higher concentrations (17% increase in CSF) of theophylline than controls to produce seizures. Tail-flick latency was slightly (19%) but statistically significantly reduced in adrenalectomized rats and lengthened (18%) in adrenalectomized, corticosterone-supplemented animals.

Adrenalectomy↗
PubMed1992

Potential pharmacodynamic effect of charcoal on theophylline neurotoxicity in normal rats.

Previously, it has been found that repeated oral administration of activated charcoal (AC) to rats with renal failure markedly decreased the sensitivity of the CNS to the neurotoxic-convulsant effect of theophylline. The present study was designed to investigate whether this effect also occurs in normal rats. Normal rats received AC per os in either a single dose or in six doses every 8 h. Control animals received equal volumes of water. Two hours following the last AC dose, animals were infused IV with theophylline until the onset of maximal seizures. Although rats pretreated with repeated administrations of activated charcoal required a larger total theophylline dose to induce convulsions, the theophylline concentrations in the serum and brain at the onset of the neurotoxic episode were not affected by the charcoal pretreatment. It is, therefore, concluded that the gastrointestinal dialysis produced by the activated charcoal had no apparent effect on theophylline-induced neurotoxicity in normal rats.

Animals↗
PubMed1992

High-dose methotrexate does not affect the pharmacodynamics of phenobarbital hypnotic action but decreases the central nervous system (CNS) sensitivity to pentylenetetrazol-induced maximal seizures in rats.

Chemotherapy with high-dose methotrexate (HD-MTX) is often associated with acute neurotoxicity. We determined whether the altered neuronal function after HD-MTX [such as the reduced regional cerebral metabolic glucose rate (rCMRGlc) and slow electroencephalographic pattern] affects the sensitivity of the CNS to centrally acting drugs: the depressant phenobarbital, which reduces rCMRGlc, and the analeptic agent pentylenetetrazol (PTZ), which elevates rCMRGlc. Adult male Sabra rats received an i.v. infusion of MTX, 0.51 mg/min, to induce neurotoxicity or saline solution for 24 hr. Subsequently, MTX-treated and control groups were infused in one experiment with phenobarbital until loss of the righting reflex and in the second experiment with PTZ until the onset of maximal seizures. HD-MTX did not affect the infused hypnotic dose or serum, brain, and cerebrospinal fluid concentrations of phenobarbital at the onset of anesthesia. The convulsive dose and PTZ concentrations in the serum and brain at the onset of maximal seizures were significantly higher in the HD-MTX-treated animals. These outcomes indicate that HD-MTX and the reduced rCMRGlc that follows this treatment do not contribute to the hypnotic action of phenobarbital. On the other hand, treatment with HD-MTX exhibited anticonvulsant properties as evidenced by the reduced CNS sensitivity to PTZ-induced seizures.

Animals↗