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Biomedical subjects

J Hamer

Publications and source records attributed to J Hamer.

At least 19 recordsLinked to original sources

Percentage of Philadelphia chromosome (Ph)-negative and Ph-positive cells found after autologous transplantation for chronic myelogenous leukemia depends on percentage of diploid cells induced by conventional-dose chemotherapy before collection of autologous cells.

We collected peripheral blood mononuclear cells and bone marrow cells soon after recovery from conventional-dose chemotherapy-induced myelosuppression and transplanted these cells into advanced chronic myelogenous leukemia (CML) patients after treating these patients with 120 mg/kg cyclophosphamide, 750 mg/m2 VP-16, and 1,020 cGy of total body irradiation (TBI). Of the 10 late chronic-phase patients and the eight accelerated-phase CML patients evaluable posttransplant, 90% and 87%, respectively, remain alive posttransplant, whereas none of the three blast crisis CML patients given this therapy remain alive posttransplant. We measured the percentage of Philadelphia chromosome (Ph)-negative cells in the autologous cells collected after conventional-dose chemotherapy-induced myelosuppression before autologous transplant and in the marrow of these same CML patients after autologous transplantation of these cells into recipients treated with the cyclophosphamide, VP-16, and TBI. A direct correlation (correlation coefficient = 0.91) was observed between the level of Ph+ cells in the transplanted cells and the percentage of Ph+ marrow cells after transplant in 21 patients so transplanted. The data show that the chance of generating cytogenetic remissions post-transplant depends on the percentage of diploid cells in the preparations of autologous cells used for transplant and the stage of disease of the patients at the time of collection of the autologous cells.

Adult

The acute changes in serum binding of disopyramide and flecainide after myocardial infarction.

In the serum basic drugs are principally bound to alpha1-acid glycoprotein (AAG). Following acute myocardial infarction it has been shown that the levels of AAG rise. The serum levels of total protein, albumin, AAG and the protein binding of 2 antiarrhythmic drugs which are bases, disopyramide and flecainide, was measured in vitro with blood samples from eleven patients taken over the first 5 days following myocardial infarction. Mean AAG levels significantly increased from 1.04 g/l on Day 1 to 1.80 g/l on Day 5. The binding of disopyramide, which is highly bound, rose from 80% to 87%, representing a 35% decrease in free drug concentration. In contrast the binding of flecainide fell from 61% to 53%, a 20% increase in free drug concentration. These data suggest that although the binding of strongly bound drugs responds appropriately to increases in binding protein after acute myocardial infarction, poorly bound drugs are displaced from binding sites possibly by endogenous substances. Since the pharmacological effects of a drug are related to its free (unbound) concentration, the changes in the proportions of free to bound drug after myocardial infarction may have important clinical implications.

Aged

Cardiac arrhythmias during cytotoxic chemotherapy: role of domperidone.

Four patients receiving platinum-containing chemotherapy were treated with domperidone (20 mg) by slow intravenous injection followed by a continuous infusion for 24 h at a dose of 10 mg 24 h-1 kg-1. Cardiac monitoring and plasma potassium and domperidone concentration measurements were performed. Severe cardiac arrhythmias occurred in two patients. A control group of 14 patients treated with similar chemotherapy, without domperidone, also underwent cardiac and plasma potassium monitoring. No significant arrhythmias were seen. The electrophysiologic effects of domperidone are discussed. It is concluded that treatment with intravenous domperidone is associated with the occurrence of cardiac arrhythmias.

Antineoplastic Agents

Development of ganglioglioma in computed tomography.

A 2-year computed tomographic progress investigation in a young, female patient with a history of attacks over several years with final histological verification of ganglioglioma is presented. Although there are evidently no absolute pathognomonic signs of this rare intracranial tumor in the CT scan, together with the age of the patient, the tumor localization and the clinical history, CT findings can suggest the tentative diagnosis of a ganglioglioma pre-operatively. The case communicated here is so far the only one in the scanty CT literature on gangliogliomas in which the space-occupying development of this tumor (it was mainly cystic) could be exactly documented.

Adolescent

Extradural spinal meningiomas. Report of two cases.

Extradural spinal meningiomas are infrequent. The relevant clinical literature and the present case histories demonstrate that purely extradural meningiomas do not essentially differ from the common intradural types. They show the same histology, the same frequent location in the thoracic spine and the well-known sex preponderance of female patients. During operation, an extradural meningioma may easily be mistaken for a spinal metastasis. Intraoperative histology is, therefore, decisive for adequate surgical treatment. The resection of the tumour should include a generous excision of the adjacent dura.

Aged

Observations on the biphasic nature of digitalis electrophysiological actions in the human right atrium.

Cardiac electrophysiological effects of a digitalis glycoside have been investigated by right atrial intracardiac stimulation and recording in 12 patients with paroxysmal supraventricular tachyarrhythmias. Measurements were made of atrial effective refractoriness by pacing together with programmed premature extrastimulation. Simultaneous recordings of atrial action potential duration from a site close to the sinoatrial node and from a more distal atrial site were made using an endocardial contact-injury potential technique. All subjects received methyldigoxin 10.0 micrograms X kg-1 intravenously, while half were also pretreated with atropine. A biphasic response to methyldigoxin was observed, with initial action potential prolongation, maximal at 20 min post-infusion, followed by significant action potential shortening which persisted to the end of the study period at 40 min. The initial phase, that of prolongation, was associated with smaller increases in atrial effective refractoriness and increased vulnerability to atrial tachyarrhythmia initiation. During the subsequent phase of action potential shortening, the gap between the termination of effective refractoriness and completion of action potential repolarisation was narrowed, coinciding with diminished vulnerability to tachyarrhythmias. Slight but significant atrioventricular conduction delay was apparent 30 to 40 min after glycoside infusion, indicating enhanced vagal activity during the phase of action potential shortening. Prior atropinisation reduced the magnitude of both early and late components of the biphasic action potential response to digitalis, supporting the proposition that both components are mediated via cardiac muscarinic receptors. Since vagal effects on the atrioventricular junction appeared during the later phase, it is suggested that initial action potential prolongation by digitalis may have been effected via local acetylcholine release, while subsequent action potential shortening may have been caused by a combination of vagally and locally mediated activity.

Action Potentials

Relationship between myocardial uptake and actions in heart failure of methyldigoxin.

1 Problems have been encountered in recent years in confirming useful benefit to patients with heart failure and sinus rhythm from acute exposure to digitalis glycosides, though effectiveness of these preparations upon cardiac contractile performance is indisputable. Undesired effects such as those upon systemic vascular resistance have been invoked to explain this. 2 Detailed haemodynamic responses have been studied by cardiac catheterisation in nine such patients for 30 min after intravenous methyldigoxin infusion. Myocardial glycoside uptake was simultaneously assessed. 3 Methyldigoxin uptake by the heart was rapid, passing its peak within 20 min, and was followed by substantial elution. 4 A small progressive and significant increase in cardiac output was observed, though left ventricular filling pressures were not significantly reduced after methyldigoxin. Cardiac contractile function as assessed by left ventricular maximum dP/dt, measured in six patients, showed consistent improvement.

Cardiac Catheterization

The value of spinal computed tomography in diagnosis of herniated lumbar discs.

In this study the diagnostic value and topographical accuracy of spinal computed tomography (CT) in hte preoperative diagnosis of lumbar disc herniations were tested in 36 patients with surgically proven herniated discs. All patients also underwent metrizamide myelography. CT findings and myelograms were compared and correlated with the surgical observations. Especially in demonstrating exact diagnosis (lateral or more medial protrusion), and in showing the extent of upward or downward displacement of free disc material, CT provides valuable preoperative information. As a non-invasive diagnostic procedure, spinal CT scan may replace lumbar myelography in many patients with radicular lumbar pain.

Humans

Prognosis of oculomotor palsy in patients with aneurysms of the posterior communicating artery.

In patients with symptomatic aneurysms of the posterior communicating artery, the prognosis of oculomotor palsy mainly depends on the interval between the onset of palsy and the time of operation, and furthermore on the degree of preoperative deficit and the development of the cranial nerve lesion. The incidence of ultimately complete or incomplete palsy is the same in cases with subarachnoid haemorrhage and without rupture ("warning symptom"). In many cases, an initially incomplete paresis develops to a complete ocular palsy within eight days. Ptosis is generally the first symptom, and it frequently shows the earliest recovery of all other disturbed oculomotor functions after surgery. Full recovery of oculomotor palsy occurs usually only in those patients who undergo early clipping of an aneurysm, i.e. mainly within 10 days after onset of ocular palsy. Complete restitution after carotid ligation is possible, but rare. In cases with full recovery, restitution occurs mostly within three months, sometimes even within a few weeks. An improvement in oculomotor palsy is still possible after a year, but ultimately in these patients recovery remains always more or less incomplete. Incomplete restitution of a third cranial nerve lesion is very often associated with aberrant regeneration and subsequent synkinetic ocular movement. The restitution of the single ocular muscle functions shows a fairly constant course: the levator palpebrae muscle and the M. rectus medialis show rapid recovery. The parasympathetic fibres follow next, but normal function of elevation and depression of the ocular bulb (M. rectus sup., M. obliquus inf. and M. rectus inf.) is often delayed.

Cerebral Arteries

Chromosomal variants and male fertility.

One hundred and forty-seven healthy men were investigated to determine whether there was an association between chromosomal variants and decreased fertility. Modern chromosome banding techniques detected normal variant karyotypes in 22 (15%) of these men. The fertility parameters of the 125 men with 46,XY karyotype were compared with those of the 22 men in the variant group. Analysis of the results showed that the two groups were not biologically different with respect to semen analysis and reproductive hormone levels.

Chromosome Banding

Systemic availability of oral verapamil and effect on PR interval in man.

1 The plasma levels of verapamil and its major metabolite norverapamil were related to its effect as a Ca-antagonist on atrio-ventricular (AV) conduction, judged from prolongation of the PR interval in six normal volunteers. 2 Intravenous administration (0.1 mg kg-1) was compared to oral administration (120 mg) in each subject. 3 Intravenous verapamil showed a mean distribution half-life (alpha) of 8.5 min and elimination half-life (beta) of 2.0 h. The volume of distribution was about 112.1. Oral dosage gave an elimination half-life of 2.7 h, and a norverapamil half-life which averaged 4.6 h. The bioavailability of the oral dose averaged 22% (17 to 29%). 4 After the oral dose the percentage change in PR interval in the five appropriate subjects correlated significantly with the log plasma verapamil level (r = 0.732), but not with the log plasma norverapamil level (r = 0.078); norverapamil could not be detected after the intravenous dose. One subject developed Wenckebach type second degree AV block after each dose.

Administration, Oral