Bart Chernow

Carcinomatous involvement of the pleura: An analysis of 96 patients

Abstract To better define the prevalence, presentation, primary sites and survival of patients with Carcinomatous involvement of the pleura, we reviewed 96 cases of carcinoma of the pleura diagnosed by cytopathology or closed pleural biopsy at Colorado General Hospital from 1960 to 1975. Carcinomatous pleura) metastasis was present in 43/100,000 persons admitted to the hospital. The most common primary sites were lung in 32 of 96 (33 per cent), breast in 20 of 96 (20.9 per cent), ovary in nine of 96 (9.3 per cent) and stomach in seven of 96 (7.3 per cent). The incidence of pleural metastasis per type of carcinoma was lung in 32 of 459 (7.0 per cent), stomach in seven of 195 (3.6 per cent), breast in 20 of 645 (3.1 per cent) and ovary in nine of 303 (2.9 per cent). Chief presenting symptoms included dyspnea (57 per cent), cough (43 per cent) and chest pain (26 per cent); however, 22 of 96 subjects (23 per cent) were asymptomatic. Ninety-two per cent of the lung, breast and ovarian malignant effusions were ipsilateral to the primary lesion. The malignant pleural effusions were usually clear or serosanguineous exudates with a protein content of 3.7 ± 0.2 g/100 ml (mean ± standard error of the mean (SEM); lactic dehydrogenase 134 ± 15 lU/liter; glucose 120 ± 13 mg/100 ml, white blood cell count 2,250 ± 400/mm 3 . Mean survival was 3.1 ± 0.5 months (after diagnosis of pleural metastasis) with 54 per cent mortality within one month and 84 per cent mortality by six months. A malignant pleural effusion provided the basis for the first diagnosis of cancer in 44 of 96 patients (46 per cent). Pleural involvement, although often asymptomatic, is an ominous finding usually representing widespread metastases. Lung, breast, ovary and stomach were the most frequent primary sites, with carcinoma of the lung being the most common to involve the pleura; however, its incidence was relatively low. A malignant pleural effusion frequently represents the first evidence of cancer.

Hypomagnesemia is common following cardiac surgery

Hypomagnesemia is a common disorder in noncardiac surgical patients in the postoperative period, but the effect of cardiac surgery on serum magnesium concentrations remains unclear. The authors hypothesized that cardiac surgery is associated with hypomagnesemia, and prospectively studied 101 subjects (60 +/- 13.1 years of age) undergoing coronary artery revascularization (n = 70), valve replacement (n = 24), or both simultaneously (n = 7). Blood samples and clinical biochemical data were collected before induction of anesthesia, prior to cardiopulmonary bypass (CPB), immediately after CPB, and on postoperative day 1. Blood samples were analyzed for ultrafilterable magnesium, total magnesium, ionized calcium, parathyroid hormone, and free fatty acid concentrations. Outcome variables were also determined. Eighteen of 99 (18.2%) subjects had hypomagnesemia preinduction and this number increased to 71 of 100 (71.0%) following cessation of CPB (P less than 0.05). Patients with postoperative hypomagnesemia had a higher frequency of atrial dysrhythmias (22 of 71 [31.0%] v 3 of 29 [10.3%], P less than 0.05) and required prolonged mechanical ventilatory support (22 of 63 [34.9%] v 4 of 33 [12.1%], P less than 0.05). Hypomagnesemia is common following cardiac surgical procedures with CPB and is associated with clinically important postoperative morbidity.

Adverse effect of therapeutic vasoconstrictors in experimental acute pancreatitis.

Alpha-adrenergic drugs commonly are used to treat hypotension resulting from severe acute pancreatitis. It was shown previously that although systemic arterial pressure is increased by phenylephrine, pancreatic microcirculatory perfusion is decreased. Because inadequate tissue perfusion may be critical in the progression of edematous pancreatitis to parenchymal necrosis, it was hypothesized that vasoconstrictors might be harmful in pancreatitis. Therefore the effect of phenylephrine on cerulein-induced mild pancreatitis were studied. Sprague-Dawley rats (n = 54) were randomly allocated to 6 experimental groups and subjected to the following infusion regimens: (1) cerulein (cae) + phenylephrine (phe), (2) cae + saline (NS), (3) NS + phe, (4) cae + phenoxybenzamine (pbz) + phe, (5) NS + pbz + phe, and (6) NS. Initial and terminal hematrocrit, serum amylase activity, and blood ionized calcium concentration were determined. The animals were killed 9 hours after starting the infusion. Macroscopic and histologic changes were scored by a blinded pathologist. Phenylephrine increased the severity of cerulein-in-duced pancreatitis as manifested by statistically significant adverse changes in serum amylase, hematocrit, ionized calcium, peripancreatitic soap formation, and acinar cell vacuolization. These changes were antagonized by alpha-adrenergic receptor blockade with phenoxybenzamine. It is concluded that phenylephrine is deleterious in acute experimental pancreatitis, the first demonstration of such an effect by a pharmacologic vasoconstrictor, and suggested that microcirculatory changes may be important in the transition of mild to severe pancreatitis. Caution in the use of vasoconstrictor drugs in patients with acute pancreatitis is recommended.

Phenylpropanolamine increases plasma caffeine levels

The effects of the widely consumed drugs caffeine and phenylpropanolamine are mediated through activation of the central and sympathetic nervous systems. Severe, life‐threatening, and occasionally fatal hypertensive reactions have been reported after their combined use. This study examined the possible pharmacokinetic interaction of phenylpropanolamine and caffeine. Sixteen normal subjects received combinations of caffeine, phenylpropanolamine, and placebo. In subjects receiving 400 mg caffeine plus 75 mg phenylpropanolamine, the mean (± SEM) peak plasma caffeine concentration of 8.0 ± 2.2 μg/ml was significantly greater than after 400 mg caffeine alone (2.1 ± 0.3 μg/ml; t[24] = 2.4; p < 0.01). Physical side effects were more frequent after the phenylpropanolamine‐caffeine combination than after either drug alone or after placebo. Greater increases in both systolic and diastolic blood pressures occurred after the combination than after either drug alone. Because caffeine levels can be increased greatly when certain other drugs are coconsumed, these data indicate that phenylpropanolamine may enhance absorption or inhibit elimination of caffeine and may explain increased side effects reported after their combined use.

Transient hypertension after two phenylpropanolamine diet aids and the effects of caffeine: A placebo-controlled follow-up study☆

PURPOSE AND PATIENTS AND METHODSnReports of severe adverse reactions following the ingestion of single (75 mg) or double doses of the sympathomimetic drug phenylpropanolamine (PPA), with and without caffeine, prompted us to undertake a study of the effects of five drug preparations (75 mg PPA, 150 mg PPA, 75 mg PPA plus 400 mg caffeine, 400 mg caffeine, and placebo) in 16 resting, normotensive subjects. The study was of a double-blind, randomized, crossover design. Each subject consented to take the five drug preparations on different study days, which were separated by at least 48 hours.nnnRESULTSnCompared with blood pressure (BP) values obtained after placebo ingestion, significant BP increases occurred over several hours following 150 mg PPA and after 75 mg PPA plus 400 mg caffeine. Significant BP increases after ingestion of 75 mg PPA and after 400 mg caffeine were less frequent. The mean peak BP following 150 mg PPA was 173 +/- 9/103 +/- 4 mm Hg, compared with 148 +/- 4/97 +/- 3 mm Hg after the other three active preparations; after placebo, peak BP reached 137 +/- 8/85 +/- 5 mm Hg.nnnCONCLUSIONnThese results indicate that 150 mg PPA (the amount in two diet aids) substantially elevates BP. Our findings may explain some of the recent case reports of nontraumatic intracranial hemorrhage in young, healthy persons ingesting PPA at recommended or minimally greater dosages. We suggest physicians inform patients who are likely consumers of PPA (i.e., those with allergies, those with eating disorders, overweight persons, women during the postpartum period) and patients at risk for stroke (i.e., the elderly and hypertensive patients) of the risks of taking more than the recommended amounts of PPA and of combining caffeine with PPA.

The effects of acupuncture on operative pain and the hormonal responses to stress.

Variations in study results presented in this chapter may be attributed to a number of factors, including the population studied and type of hormonal assay used. Some researchers selected experimental groups from a population different from that used for the control group. It is unclear from the animal studies using nonacupunctured controls whether the controls received physical contacts with the experimenters comparable to those experienced by the experimental animals. The choice of acupuncture points used may also contribute to the inconsistency between experiments, since according to traditional acupuncture theory, points are not equivalent in their mediation of systemic effects. Duration of the acupuncture treatment, frequency of sampling, and time from treatment to last sample were not standardized. There is little consistency between studies even after adjustment for sampling time. Most of the statistically significant changes have been seen with electroacupuncture, and they appear to occur soon after onset of treatment, then disappear within 30 minutes of needle removal. However, the subjective changes in pain threshold have lasted several hours following needle removal. As an analgesic technique or adjuvant, acupuncture has been used most successfully in dental procedures and relatively superficial operations such as thyroidectomy; however, it has also been employed in more complex operations. The blood pressure and heart rate stability that have been observed with acupuncture analgesia have not been sufficiently explained and warrant further investigation, as does the possibility that acupuncture may be helpful in shock states characterized by increased stress hormone concentrations.

Serum prolactin concentrations in patients with the acquired immunodeficiency syndrome

Experimental evidence suggests that prolactin is an important immunomodulator hormone. Because this endocrine-immune link may represent a potential new therapeutic avenue, we considered its application in states of immunodeficiency. We hypothesized that serum prolactin concentrations might be abnormal in AIDS. To test this hypothesis, we measured serum prolactin concentrations in blood samples obtained from patients who had either AIDS (n = 15) or AIDS-related complex (n = 12), asymptomatic subjects who were antibody-positive for human immunodeficiency virus (HIV) (n = 10), HIV antibody-negative homosexual subjects (n = 10), and heterosexual HIV antibodynegative controls (n = 21). We found no difference in the serum prolactin concentrations between the five subject groups. We conclude that circulating prolactin values are not altered by HIV infection; however, the possibility that prolactin administration may modulate immune function remains to be tested. (Crit Care Med 1990; 18:440)

Hypocalcemia in experimental pancreatitis occurs independently of changes in serum nonesterified fatty acid levels

SummaryHypocalcemia and lipid abnormalities commonly occur in acute pancreatitis. Experimentally, increased plasma concentrations of free fatty acids (NEFA) can lower the serum calcium (Ca). We hypothesized that changes in blood-ionized calcium might parallel changes in NEFA concentration in pancreatitis. This hypothesis was tested in a model of severe necrotizing pancreatitis and a model of mild edematous pancreatitis. Adult male Sprague-Dawley rats (300–400 g) were randomized to receive: 100 μL sodium glycodeoxycholic acid (GDOC 34 mmol/L) infused into the pancreatic duct to produce severe necrotizing pancreatitis (Group 1); 100 μL 0.9% NaCl (NS) infused into the pancreatic duct (Group 2); Sham laparottomy (Group 3); A 6 h IV infusion of cerulein (5 μcg/kg/h) to produce mild edematous pancreatitis (Group 4); and a 6 h IV infusion of NS (Group 5). A significant time dependent decrease in blood-ionized Ca concentration, compared to normal rats, was observed in both GDOC-pancreatitis (0.836±.057 vs 1.069±.038 mmol/Lp < 0.001) and cerulein pancreatitis (0.988 ±.028 vs 1.069 ±.038p < 0.05), which was maximal 24 h after induction of pancreatitis. The degree of hypocalcemia correlated with the severity of pancreatitis (GDOC 0.836 ±.057 vs cerulein 0.988 ±.028p <.001). Hypocalcemia was not observed in any of the control groups. All experimental and control groups had significantly increased baseline NEFA concentrations compared with normal rats (p < 0.001); however, no further increase in NEFA concentration occurred in conjunction with the observed time-dependent decline in ionized calcium concentrations. Although the NEFA concentrations observed in these experiments were comparable to those measured in human acute pancreatitis (exclusive of hyperlipemic pancreatitis), the time course of the changes suggests that increases in serum NEFA concentrations in experimental pancreatitis are not the primary factor mediating hypocalcemia.

Verapamil reverses calcium cardiotoxicity

High circulating concentrations of calcium are toxic to the heart and may cause cardiac arrhythmias and arrest. To investigate the therapeutic use of calcium antagonists in hypercalcemia, we evaluated the efficacy of verapamil hydrochloride and magnesium chloride in the treatment of experimental calcium-induced cardiac arrest in laboratory rats. Verapamil rapidly reversed the experimental calcium-induced arrest and improved survival (83% survival versus 0% in controls). Magnesium failed to reverse this toxic event. We conclude from these experimental studies that verapamil may be useful in the treatment of hypercalcemic cardiac toxicity.

Pharmacologic Management of the Critically III Patient in the Perioperative Period-Emphasis on the Sepsis Syndrome

The critically ill perioperative patient requires complex pharmacologic management. The ability to measure circulating drug concentrations has helped the clinician to properly modulate therapy, especially with potentially toxic agents. Postoperative sepsis remains a difficult therapeutic problem. Controversial therapies, such as the use of corticosteroids and the utility of newer pharmacologic approaches, are beginning to be properly tested in multicenter trials. Improvements in technology (e.g., development of monoclonal antibodies), biochemistry, and pharmacology have resulted in the development of exciting, new pharmacologic avenues for the management of the critically ill perioperative patient.