Catheters: a knotty problem!
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Biomedical subjects
Publications and source records attributed to D J Jones.
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Radioreceptor assays with (-) [125I]-iodopindolol (IPIN) were used to describe circadian variations of beta-adrenoceptors in the pineal gland of male Syrian hamsters (Mesocricetus auratus). Single-point experiments (200 pM IPIN, 8-9 pineals pooled per time point) showed a significant circadian variation (p less than 0.01) with maximal values (28.9 +/- 1.8 fmol/mg protein, means +/- SEM, n = 7) between 07:00 and 02:30 h, and minimal values at 04:00 (7.2 +/- 2.9 fmol/mg protein, n = 3), 8 h after darkness onset. Either exposure of animals to light at night or treating dark exposed hamsters with a beta-adrenergic receptor blocker, propranolol, prevented the nocturnal drop in the number of beta-adrenoceptors. Scatchard analysis of saturation isotherms at 02:30, 04:00 and 08:00 h (30-600 pM IPIN, one saturation experiment with 25 pineals pooled per time point) confirmed the circadian variation.
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Transfer of the pulmonary valve to the aortic position has been used successfully by Ross for more than 20 years and in our own institution since August 1986. To expand the use of this concept to patients with root disease and/or narrow annulus, we employed the main pulmonary artery with its valve as a conduit to replace the proximal ascending aorta, reimplanting the coronary ostia into the pulmonary trunk. Seventeen patients, aged 2-62 years, underwent the procedure with three deaths. Hemorrhage precipitated each death, and there was one reexploration for control of bleeding. Postoperative echocardiography showed excellent valvular function. No anticoagulants were used except daily aspirin in three patients who underwent concomitant procedures. There were no thromboembolic episodes. Right ventricular outflow tract reconstruction was accomplished with cryopreserved aortic (three) and pulmonary (14) allograft conduits. This operation has potential for superior long-term results in complex aortic valve disease.
Bilateral adrenalectomy, like chronic pineal denervation by means of superior cervical ganglionectomy, induced an increase in the morning levels of [125I]iodopindolol (IPIN) binding to rat pineal membranes; this change may be related to the reduced input of catecholamines to the pinealocytes as suggested by the decrease in nocturnal pineal melatonin synthesis previously reported in adrenalectomized rats. Castrated rats did not show changes in IPIN binding to pineal membranes when measured either at middark or in chronically superior cervical ganglionectomized rats, suggesting that the regulation of pineal beta-adrenergic receptors is independent from gonadal control.
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alpha-Adrenoceptors in spinal cord appear to play a role in a number of physiologic processes including the control of blood pressure, pain and motor function. In order to evaluate more clearly these potential roles, the characteristics of binding of [3H]prazosin ([3H]PRZ) to spinal alpha 1 adrenoceptors and [3H]p-aminoclonidine ([3H]PAC) to spinal alpha 2 adrenoceptors were determined. Binding of each ligand to their respective adrenoceptors was saturable and Scatchard analysis revealed binding of each to a single class of adrenoceptors with characteristics of [3H]PRZ binding of Bmax = 78 fmol/mg protein and Kd = 0.75 nM and [3H]PAC binding Bmax = 70 fmol/mg protein and Kd = 1.39 nM. Whereas [3H]PRZ specific binding (Bmax) was unaltered by guanine nucleotides. [3H]PAC binding was increased with addition of 10 microM guanosine triphosphate (GTP) (P less than 0.05) and decreased with either 50 microM GTP or guanyl-5'-yl-imidodiphosphate [Gpp(NH)p] (P less than 0.01). Competition for specific [3H]PRZ and [3H]PAC binding by various alpha 1 and alpha 2 adrenoceptor agonists and antagonists of known pharmacologic activity revealed that [3H]PRZ defines alpha 1 adrenoceptors (Ki = 2.1 nM for prazosin vs 4300 nM for yohimbine) and [3H]PAC defines alpha 2 adrenoceptors (Ki = 1.06 nM for yohimbine vs 15480 nM for prazosin). Regional spinal cord studies demonstrated that dorsal spinal cord in the lumbar region contains the highest density of both [3H]PRZ (Bmax = 93 +/- 14 fmol/mg protein) and [3H]PAC (Bmax = 101 +/- 6 fmol/mg protein) binding. In contrast, lowest binding was evident in thoracic cord with equal levels in both dorsal and ventral regions (Bmax = 44-48 fmol/mg protein). The regional distribution of both alpha 1 and alpha 2 adrenoceptors in spinal cord compares to the localization previously classified functionally utilizing various pharmacological agonists and antagonists at norepinephrine receptors.
A consecutive series of 123 colorectal cancers, prospectively followed for 3 years, was studied to determine if the prognostic significance of DNA ploidy related to: (a) thresholds used to define DNA aneuploidy, or (b) aneuploid sub-groups defined by DNA index (DI) and peak size. Aneuploidy was defined using 3 methods depending on the minimum proportion of nuclei considered to constitute an aneuploid peak; type 1, 5%; type 2, 10%; type 3, 10% if DI is 1.1-1.8, but 15% if DI is 1.9-2.1. DNA aneuploidy rates were type 1, 75%; type 2, 67%; type 3, 58%. The significance of clinical and pathological correlations varied with the use of different methods. All were associated with a significant DNA diploid survival advantage which was strongest for type 3 (p = 0.006). DI was unrelated to survival irrespective of the presence or absence of an associated S/G2; 33% with a DI of 1.1-1.8 and 35% with a DI of 1.9-2.1 survived. Prognosis was inversely proportional to aneuploid peak size, 48% with small peaks (less than 20%), 30% with intermediate peaks (greater than 20% less than 40%), but none with large peaks (greater than 40%) survived (p = 0.03). We conclude that: (a) thresholds used to define DNA aneuploidy affect the prognostic significance of DNA ploidy; (b) survival is independent of the DI of aneuploid peaks; and (c) measurement of aneuploid peak size refines the prognostic value of DNA ploidy.
A simple procedure has been developed that permits measurement of beta-receptors in membrane preparations from individual rat pineal glands using [125I]iodopindolol ([125I]PIN). [125I]PIN binding to pineal membranes was stereospecific and saturable. Scatchard analysis of saturation isotherms yielded a Kd of 147.3 +/- 54 pM and a Bmax of 11.1 +/- 1.5 fmol/pineal gland. Binding was linear suggesting that [125I]PIN binds to a single population of pineal beta-adrenergic receptors. This procedure was used to evaluate 24-h variations in density of pineal [125I]PIN binding sites in male rats maintained in a 14:10 h light:dark cycle. Binding remained uniformly low during the daytime, increased slightly prior to lights off and peaked after 6 h of darkness decreasing abruptly 2 h later, before lights on. In animals maintained in light at night, the number of binding sites also increased, but did not exhibit the darkness-related decrease. The results demonstrate that beta-adrenergic receptors defined via [125I]PIN binding can be measured in tissue samples equivalent to less than one pineal gland. Moreover, the technique can be used in studies concerning the noradrenergic regulation of pineal function.
A prospective study of prognostic factors has been carried out in a group of 123 consecutive patients with colorectal cancer. The fate of all patients is known at 3 years after operation. Clinical and pathological data were recorded at the time of presentation and operation, and the patients have been subject to regular postoperative review. DNA ploidy status was determined by flow cytometry. In all, 39 (33 per cent) patients had DNA diploid tumours and 80 (67 per cent) patients had DNA aneuploid tumours. In four cases, tumour material was not obtained. The patients with DNA aneuploid tumours had a worse prognosis than those with DNA diploid tumours, but this was only seen in those patients classified as Dukes' B. In a Cox's regression analysis, the surgeon's assessment of operability was the strongest predictor of survival, followed by the pathological classification and the patient's age. After these factors had been considered, the DNA ploidy status conferred no independent survival value.
In male rats housed under a 14:10 LD cycle (lights on at 0600 h), pineal beta-adrenergic receptors, assessed as 125Iodopindolol (IPIN) binding to membrane preparations, showed a 24 hour variation characterized by a nocturnal increase that peaked around middark (2300 h-0200 h) and a decrease during the latter half of the dark period. Animals exposed to light for 3 hours into the normal dark period showed a similar increase in IPIN binding that was prevented by a single sc injection (0.5 mg/kg) of isoproterenol (ISO). The decrease in IPIN binding observed after middark was prevented both by moving the animals to light at 0200 h and by propranolol administration (20 mg/kg). Likewise, the reduction in IPIN binding was induced in light exposed animals both by ISO administration (in a dose dependent manner) and by injection of norepinephrine (NE) plus the catecholamine uptake blocker desmethylimipramine (DMI). DMI alone was without effect. Chronic denervation of the pineal gland by superior cervical ganglionectomy (SCGx) increased IPIN binding to levels not higher than those observed at middark. The results suggest that rat pineal beta-adrenergic receptors are regulated in a rhythmic 24 hour pattern. A decrease in density (downregulation) induced by a darkness-associated increase in NE release, occurs late in the night before lights on; recovery from the down regulated state (upregulation) occurs during the light and early dark phase, reaching a maximum density of beta-adrenergic receptors at middark not different from that observed in chronically denervated pineal glands.
A patient with Klippel-Feil syndrome who underwent abdominal surgery is presented and the anomaly reviewed. The anatomical abnormality and potentially unstable neck provide a potentially difficult tracheal intubation which was undertaken using an awake fibreoptic technique. The role of the fiberscope and the advantage of pre-operative assessment of the difficult airway are discussed.
Microscopic haematuria is a common finding in young men. Controversy exists as to its significance and how it is best investigated. A prospective study of 100 young men under the age of 40 with microscopic haematuria has been performed. A positive diagnosis was made in 32 patients. Cystourethroscopy was of diagnostic value in only 3 patients and of therapeutic value in a further 3. It was concluded that cystourethroscopy is of minimal diagnostic value in young men with microscopic haematuria. Its routine use is unnecessary and should be reserved for those patients in whom investigation suggests that a treatable cause may be found in the lower urinary tract.
Fifty three bronchopulmonary carcinoid tumours were studied to assess the significance of DNA ploidy, determined by flow cytometry of paraffin embedded tissue. Twenty eight were typical carcinoid tumours and 25 well differentiated neuroendocrine carcinomas. Twenty seven were DNA diploid and 26 DNA aneuploid. DNA aneuploidy was significantly associated with histological features of increased malignant potential. Survival data were available for 43 patients. Of the 19 with DNA diploid tumours, 16 survived five years, compared with 14 of 24 with DNA aneuploid tumours--the difference being at the borderline of statistical significance. In a Cox multivariate regression analysis with other histological variables, DNA ploidy did not confer independent prognostic information. It is concluded that, although DNA aneuploidy as determined by flow cytometry is an indicator of increased malignant potential in bronchopulmonary carcinoid tumours, it does not provide clinically useful information additional to the results of routine histological examination.
Two cases of apparently congenital bulbar urethral stricture occurring in brothers are presented. Such a finding has been rarely reported. Congenital strictures may be more common than previously thought and a full history is essential in such cases when the aetiology remains uncertain. Biopsy of the stricture may be of value.
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The present study reports the existence of high-affinity [3H]nitrendipine ([3H]NIT) binding sites in rat spinal cord. Characterization studies revealed [3H]NIT binding to synaptosomes to be specific, rapid and saturable, occurring at a single population of sites. The Bmax was 51 fmol/mg of protein and Kd 0.22 nM with a Hill slope of 0.96. Studies with nifedipine and verapamil demonstrated that the latter binds to a site allosterically linked to the 1,4-dihydropyridine binding sites in spinal cord. The Ca++ channel agonist methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)-pyridine-5 carboxylate acted competitively at the 1,4-dihydropyridine binding site and inhibited specific [3H]NIT binding completely. Organic Ca++ antagonists inhibited binding to various degrees. Treatment with EDTA reduced specific [3H]NIT binding in spinal cord by 83%. This was restored by externally added Ca++. The effect of various mono-, di- and trivalent cations on specific [3H]NIT binding as well as its restoration in EDTA-treated preparations was tested. Na+, K+, Li+, Ca++, Mg++, Mn++ and Ba++ were found to have no significant effect. Other cations inhibited binding of [3H]NIT in the sequence La greater than Cd++ greater than Cu++ greater than Co++. Regional studies in rat spinal cord demonstrated 3-fold higher specific [3H]NIT binding sites in the dorsal cord compared to the ventral cord. Moreover, further variations were also found in cervical, thoracic and lumbar regions of the spinal cord. The results demonstrate that binding of the labeled calcium antagonist in spinal cord membranes is of high affinity and completely reversible.(ABSTRACT TRUNCATED AT 250 WORDS)
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