General Clinical Impression Research Articles

Coronary Artery Bypass in Asian Patients

Coronary artery disease in Asians deserves far more attention than it has received in the literature to date. Most of the available reports focus on immigrants from the Indian subcontinent. These immigrants have a significantly higher risk of coronary artery disease than either their compatriots who do not emigrate or the indigenous population of their adopted countries. This finding cannot be explained on the basis of standard coronary risk factors. There is a general clinical impression that Asians of all nationalities have smaller coronary arteries and more diffuse coronary disease than other ethnic groups; therefore, they are less suitable candidates for conventional bypass grafting. This impression remains a source of controversy. Our experience at the Texas Heart Institute indicates that, after coronary bypass surgery, early and long-term results in Asians are as satisfactory as in other ethnic groups. However, much more research is needed to explain the many paradoxical aspects of coronary disease in Asian patients.

Brain mapping in thinking and language function.

Regional cerebral blood flow, rCBF, is coupled to regional cerebral metabolism and changes in rCBF reflects changes in neuronal activity. rCBF studies have provided information about the functions of a great number of cortical regions in the normal human brain. Outside the motor areas and sensory association areas there are areas committed to the transformation of information retrieved or generated within the brain itself. Language is processed within these regions. In contrast to the general clinical impression the functional mapping methods reveal that there is a large number of cortical regions activated bilaterally during language processing. Pure intrinsic brain work causes a profound activation of the cerebral cortex. Different types of thinking are seen to activate different sectors of the cortical space.

Verapamil in affective disorders: A controlled, double-blind study

Eighty-six depressed inpatients were divided into four groups: patients in each of three groups were treated, respectively, with identical capsules of verapamil, amitriptyline, or placebo, whereas the fourth group was treated eclectically by the ward physician with so-called state-adjusted treatment (SAT). Each treatment period lasted 5 weeks. Psychopathology was assessed with the Hamilton Rating Scale for Depression, by the Zung selfrating scale, by the 100-mm analog scale, and by general clinical impression. Results indicated that amitriptyline and SAT were superior to verapamil or placebo. There was no significant difference between verapamil and placebo or between SAT and amitriptyline. This finding was more definitive in the homogeneous subgroup of 55 women with DSM-III diagnosis of Major depression. In addition, 12 manic inpatients (DSM-III) were treated orally with verapamil, 24 with neuroleptics, and 11 with both neuroleptics and lithium carbonate. The decline of their psychopathology, assessed by the Brief Psychiatric Rating Scale (BPRS) and general impression, was fully comparable. Using Analysis of Variance (ANOVA), the statistical difference among courses of psychopathology expressed as total BPRS scores reaches borderline significance in favor of verapamil. In contrast to neuroleptics, verapamil did not induce any sedative, hypnotic, or cataleptic effects, and was well tolerated.

Calcium channel antagonists, Part I: Fundamental properties: mechanisms, classification, sites of action.

Ca2+ channel antagonists are agents that interact with the voltage-dependent Ca2+ channel in a highly specific way. The prototype agents of cardiovascular importance are verapamil, nifedipine, and diltiazem, in historical order of appearance. These agents all have different molecular structures and bind separately with receptor sites located in or near the calcium channel, at molecular sites still to be fully identified. There are probably three distinct receptor sites (V, N, D) which stand in relation to the "gate" of the long-acting "L" calcium channel. There is probably overlap among the receptor sites, especially between the V and D sites to explain their common properties. All three agents inhibit the voltage-dependent calcium channel in vascular smooth muscle and also myocardial slow calcium channels. The ratio of the arterial to the myocardial effect is an index of the arterial selectivity, generally held to be a desirable property because the negative inotropic effect is usually a liability. The general clinical impression that nifedipine is the agent most active in vascular tissue in relation to the myocardial effect is supported by data on the relative potencies of these three agents on blood perfused dog preparations and by a comparison of the potency on rat vascular (portal vein) versus myocardial effects. Nonetheless all three agents are highly active in the inhibition of K(+)-induced vascular contractions (nifedipine 10(-9) M to 10(-8) M; verapamil 10(-7) M to 10(-6) M; and diltiazem 5 x 10(-7) M to 10(-6) M; concentrations for 50% inhibition of K(+)-induced vascular contractions in rat or rabbit aorta; comparative data for resistance vessels not available). The clinical impression that verapamil and diltiazem are more active on nodal tissue is also supported by a comparison of potencies on blood perfused dog nodal preparations in comparison with effects on coronary flow, with verapamil and diltiazem being approximately 10x more potent on the AV node than increasing coronary blood flow, so that the nodal effect is first detected. These basic pharmacological properties explain why all these three agents have clinical effects relevant to inhibition of vascular contraction (antihypertensive and antianginal effects) and only verapamil and diltiazem have clinically relevant inhibitory effects on the AV node (inhibition of supraventricular tachycardias). The comparative potencies of verapamil, diltiazem, and nifedipine in angina and hypertension will be examined in Parts II and III of this review.

Ultrastructural Abnormalities in Increased-Permeability Pulmonary Edema

A general clinical impression is that increased microvascular permeability following acute lung injury always leads to pulmonary edema. The ARDS is a final pathway of acute lung injury. A number of agents may initiate acute lung injury, either directly or indirectly, via cellular and humoral mediators. Clinical and experimental animal studies indicate that both the microvascular and alveolar-airway barriers are susceptible to injury. Unfortunately, the spectrum of cellular damage is nonspecific and quite uniform, regardless of the injurious agent. Thus pathologic examination often reveals little about the exact underlying etiology of the lung injury. This situation has minimized the diagnostic value of lung biopsies in clinical cases of increased-permeability pulmonary edema. Nonetheless, the pathologic information has been, and will continue to be, invaluable to understanding the structural and functional relationships present in experimental models of increased-permeability pulmonary edema.

Racial variations in electrocardiograms and vectorcardiograms between black and white children and their genesis

Despite a general clinical impression that the ECG of black children differs from that of white children, none of the normal standards in children have taken race into consideration. Biographic data, blood pressure, hemoglobin, ECG, Frank VCG and echocardiogram were obtained in 244 normal children (124 blacks and 120 whites) aged 3-17 years and 144 measured parameters and 57 computed variables were analyzed. The children were divided into age groups of 3-5, 6-10, 11-14, and 15-17 years. The 15-17 year age group was small and therefore excluded. In the 3-5-year age group there were no sex differences (p greater than 0.05) nor were there any differences (p greater than 0.05) observed between black and white children. No significant sex differences were seen in 6-10-year-olds. However, the amplitude of the R wave in lead I, S in V1 and V4, and the sums of SV1 and RV6 as well as SV1 and RV5 on the ECG, and X to the left and Y to the inferior on VCG were greater in black than in white children (p less than 0.01). In 11-14-year-olds many sex-related differences were seen in each race. R in leads I, II, AVL, AVF and V4, S wave in V1 and V4R, and the sums of SV1 and RV5 as well as SV1 and RV6 in the ECG, and Y inferior and Z anterior in the VCG were higher (p less than 0.01) in black males than white males. However, no differences (p greater than 0.05) were observed between black and white 11-14-year-old girls. To understand the causes of these differences, comparisons of the biographic data, blood pressure, hemoglobins and echocardiograms were made. The height, weight, body surface area, chest circumference, AP diameter of the chest, and diastolic and systolic blood pressure were similar (p greater than 0.1) in all groups. The hemoglobin level was lower in black than white children (p less than 0.05). However, this difference was seen in all age-sex subgroups, suggesting that hemoglobin level was not responsible for the ECG-VCG differences. The LV posterior wall in diastole was thicker and the anterior chest wall to mid-LV distance was shorter in black than in white children in age-sex subgroups in which ECG-VCG differences were observed.(ABSTRACT TRUNCATED AT 400 WORDS)

164 ELECTROCARDIOGRAPHIC DIFFERENCES IN BLACK AND WHITE CHILDREN

Despite a general clinical impression that the electrocardiogram (ECG) of black (B) children differs from that of white (W) children, none of the normal standards in children have taken race into consideration. Biographic data, ECGS, Frank vector-cardiograms (VCGs), and echocardiograms were obtained in 204 normal children (B-97, W-107) ages 3-17 yrs and 144 measured parameters and 57 computed variables were analyzed. The children were divided into 3-5, 6-10, 11-14 and 15-17 yr age groups. In each race, sex related differences were found in the 11-17 yr age group and none were observed below 10 yrs of age. There were no ECG differences (p>0.05) between races in the 3-5 yr olds and few minor differences in 6-10 yr old children. However, major differences were observed in the 11-17 yr olds. The VCG data were similar. The height, weight, body surface area, blood pressure, hemoglobin, chest circumference and AP diameter of the chest were found to be similar (p>0.1) in both B and W children. However, left ventricular (LV) posterior wall (PW) thickness, interventricular septal thickness and anterior chest wall (ACW) to mid-LV distance or LV muscle mass were different (p<0.5 to <0.01) in the age sex groups with ECG differences. These data confirm the previously suspected ECG differences in B and W children. This difference appears related to the quantitive differences in LV muscle or to the depth of the LV from ACW. It is suggested that separate normal standards should be used for evaluation of ECG voltage in B and W children beyond 6 yrs of age.

Dantrolene Sodium

Dantrolene sodium or dantrolene1 is 1([5-(nitrophenyl)furfurylidend] amino) hydantoin sodium hydrate. It is indicated for use in chronic disorders characterised by skeletal muscle spasticity, such as spinal cord injury, stroke, cerebral palsy and multiple sclerosis. Dantrolene is believed to act directly on the contractile mechanism of skeletal muscle to decrease the force of contraction in the absence of any demonstrated effects on neural pathways, on the neuromuscular junction, or on the excitable properties of the muscle fibre membranes. Controlled trials have demonstrated that dantrolene is superior to placebo in adults or children with spasticity from various causes, as evidenced by clinical assessments of disability and daily activities, and by muscle and reflex responses to mechanical and electrical stimulation. It is somewhat less effective in patients with multiple sclerosis than in those with spasticity from other causes. There has been a general clinical impression in controlled trials that dantrolene caused less sedation than would have been expected from therapeutically comparable doses of diazepam. In 2 controlled trials, there was no significant difference between dantrolene and diazepam in terms of reductions in spasticity, clonus, and hyperreflexia, but side-effects such as drowsiness and inco-ordination occurred significantly more frequently on diazepam. Long-term studies have indicated continuing benefit for patients taking dantrolene, though the incidence of side-effects has often been high and there has been a suggestion of exacerbation of seizures in children with cerebral palsy. Dantrolene may be of value in the medical treatment of spasm of the external urethral sphincter due to neurological and non-neurological disease, and animal studies suggest a potential use in the management of malignant hyperpyrexia. Chemical evidence of liver dysfunction may occur in 0.7 to 1% of patients on long-term treatment with dantrolene, with symptomatic hepatitis in 0.35 to 0.5% and fatal hepatitis in 0.1 to 0.2%. The drug commonly causes transient drowsiness, dizziness, weakness, general malaise, fatigue and diarrhoea at the start of therapy. Muscle weakness may be the principal limiting side-effect in ambulant patients, particularly in those with multiple sclerosis, and therapy could be hazardous in patients with pre-existing bulbar or respiratory weakness. The dosage of dantrolene has been fixed in most controlled trials, though long-term studies have indicated the need for individualisation of dosage. The initial dose is usually 25mg once daily, increasing to 25mg two, three or four times daily, and then by increments of 25mg up to as high as 100mg two, three or four times daily. The lowest dose compatible with optimal response is recommended.

Low-dose clonidine: a review of its therapeutic efficacy in migraine prophylaxis.

The demonstration that long-term administration of relatively low doses of clonidine decreased the responsiveness of blood vessels to vasodilator and vasoconstrictor drugs in animals led to its investigation in the prevention of migraine in man. Results of placebo-controlled and open therapeutic trials have shown that clonidine in low dosages (75 to 150 mug daily) is useful in preventing migraine headaches in about 30%-50% of patients. A 50% or greater reduction in headache frequency or headache indices has been reported in 40% of patients in controlled and open studies. Thus clonidine, like other drugs used in the interval therapy of migraine, can be expected to be effective in only a proportion of patients. Although clonidine has not been compared directly with other drugs used in the prophylactic treatment of migraine, the general clinical impression is that it is less effective then pizotifen or methysergide. Because it is relatively well tolerated at dosages of 75 to 150 mug daily it is worthy of a trial, particularly in patients considered to need prophylactic migraine therapy for the first time, and when migraine occurs in association with hypertension. At the dosages used in migraine prophylaxis, which are almost invariably lower than used in hypertension, clonidine does not cause hypotension and can be used in patients with cardiovascular disease. The principal side-effects are drowsiness and dry mouth which tend to diminish as treatment continues.

Ulcerative colitis beginning in childhood.

Ulcerative colitis is not frequent in childhood, but there is a general clinical impression that, when it does occur in children, it frequently runs a severe course. It is therefore valuable to have the sort of study on prognosis reported by Devroede and his colleagues in this number of the Journal (p 17). It is a measure of the wealth of clinical experience at the Mayo Clinic that the authors have been able to assemble no fewer than 396 subjects seen while children at the Clinic from 1919 to 1965 in whom the diagnosis of ulcerative colitis was firm. The . . .

Carcinoma of the prostate: Analysis of patient morbidity at the 6-month, 12-month and 18-month follow-up examinations

The Veterans Administration Cooperative Urological Research Group is engaged currently in a prospective study of carcinoma of the prostate. This is the first report of the progress of the study since its initiation. There are four stages of this disease. However, this report deals almost exclusively with Stage III and Stage IV patients, i.e. patients with advanced disease. There are four treatments (orchiectomy + estrogen, orchiectomy alone, estrogen alone, and placebo alone) to which the patients are randomly assigned. Patients are allocated to either estrogen or placebo so that neither patient nor clinician is aware of what drug the patient receives. Preliminary results show that patients receiving orchiectomy + estrogen, orchiectomy alone, or estrogen alone exhibit a better over-all response than do those patients receiving placebo alone. This pattern persists up to and including the 18-month follow-up examination. There appears to be excellent correlation between General Clinical Impression— the clinician's subjective appraisal of the patient—and Over-all Response—the objective appraisal of the patient—for all stages and treatment groups at all three follow-up examinations with the exception that clinical appraisal seems to be some-what over-optimistic in that only approximately 40 per cent of the patients with increasing disease (the objective measure of response) are judged to be clinically worse.

Depth dose curves for grids in x-ray therapy.

The use of treatment grids (i.e., radiopaque material with alternate open and closed areas) in x-ray therapy requires depth dose information not given in the conventional depth dose tables. It is the purpose of this paper to show that the essential information can be derived from these tables. A detailed analysis of the grid depth doses will be presented which tends to corroborate the general clinical impression that the function of the grid is to preserve areas of the skin, which will serve as centers of regrowth, while still delivering adequate and sufficiently homogeneous radiation at a depth. The use of deep therapy treatment grids and an understanding of their effect on the distribution of radiation are not new. As early as 1909 Köhler (1) proposed the use of a grid as a method of delivering a deep tumor dose while protecting against radiodermatitis. In 1925 Abeles (2) discussed the distribution of radiation for a grid from a geometrical point of view (without, however, considering the effect of scattered radiation). In 1933 Liberson (1, 3), who was not aware of the previous work, published depth dose measurements and animal and clinical studies with “multiperforated screens” essentially the same as those being reported here. His back-scatter and depth dose measurements were made with ionization chambers sufficiently large so that they averaged over both the maxima and minima in radiation dose-rate. His measurements verified his expectation that the ratio between the average dose-rate with and without the grid equals the ratio of the open area of the grid portal to the total area. He concluded that, “since the remote effect upon the skin of both rabbits and man is the same when three or four times as much radiation is delivered through the perforator as without it, the underlying tissue actually receives one and a half to two times as much radiation with the perforator as without it.” This statement summarizes essentially our present view on the depth dose effect of the treatment grid. Similar reports followed in 1934, by Haring (4) and Woenckhaus (5). In 1945, Grynkraut (6) described biological and clinical experiments with a lead grill having 3 × 3-cm. openings separated by 5 mm. of lead. He made photographic tests of the dose distribution and showed that the sharp picture of the grill obtained on a film at a distance of 10 cm. in air was greatly blurred when water was placed between the grill and the cassette. He concluded that the grill “prevents the vasomotor phenomena of erythema” by protecting areas of the skin, while still giving a more or less homogeneous dose at a depth. He advised that the x-ray air dose must be doubled when using the grill. In 1949, Jolles (7) reported the clinical use of an “alternating chessboard” type of treatment grid. Part of the treatment was given through a certain grid, and the remainder through a complementary grid.

SKIN AND BODY TEMPERATURES OF SCHIZOPHRENIC AND NORMAL SUBJECTS UNDER VARYING ENVIRONMENTAL CONDITIONS

Investigations of the physiologic concomitants of the schizophrenic psychosis have suggested a certain degree of dysfunction of the autonomic nervous system. 1 It has been difficult, however, to obtain unequivocal experimental data by which to determine the matter. Since the autonomic nervous system controls the responsiveness of the thermoregulating mechanisms, it has been attempted in the following series of studies to determine the state of the former through the physiologic reactions of the latter. There have been reported heretofore no accurate studies under controlled conditions of skin temperature in schizophrenic subjects. It is the general clinical impression that subjects suffering from this psychosis have cold and clammy extremities. Finkelman and Stephens 2 reported a greater fall in body temperature in schizophrenic than in nonpsychotic subjects on exposure to cold baths. Gottlieb and Linder 3 found a greater increase in body temperature in schizophrenic than in normal persons after exposure to

INSULIN INACTIVATION BY HUMAN BLOOD CELLS AND PLASMA IN VITRO

THE EFFECT OF INFECTION ON INSULIN ACTIVITY The inhibitory action of blood cells and plasma in vitro on insulin activity in the rabbit1offered a new means of study of the long known fact that infection has a severe and detrimental effect on the ability of the body to metabolize foods properly, especially foods containing the carbohydrates. This has been demonstrated both for the diabetic and for the nondiabetic person.2Insulin given to a person with an infection has less effect in lowering the blood sugar than it does on a normal person. During such periods, the sugar tolerance is diminished and, according to Richardson and Levine,3carbohydrate oxidation is diminished. Explanation for this failure of insulin to have its usual effect during infection has been varied. The general clinical impression that, due to actual pancreatic injury, an inadequate supply of insulin is produced, is not very likely since exogenous