Gonadotropin-releasing hormone agonistic analogues in the treatment of advanced prostatic carcinoma

Orchiectomy or chronic administration of the gonadotropin releasing hormone agonistic analogue D, Ser (TBU)⁶, des Gly-NH₂¹⁰ ethylamide (HOE 766) were employed as therapeutic maneuvers in 25 patients with advanced prostatic carcinoma. HOE 766 administration effectively suppressed plasma testosterone to castrate levels that persisted for as long as treatment continued. Surgical and medical castration resulted in a significant decrease in prostatic size; this became evident earlier for surgically than medically treated patients (P <.05), but no difference existed after the third month of treatment. Symptoms and signs of prostatism improved in practically all the patients. Among patients with stage D₂ disease, there was an improvement in five as far as bone radiological assessment was concerned. Alkaline phosphatase levels did not show appreciable changes in patients showing objective stable disease or partial response according to National Prostatic Cancer Project criteria. Radioimmunoassayable prostatic acid phosphatase levels became normal in two of two stage C, five of five stage D₁, and eight of seventeen patients with stage D₂ disease, a rise in prostatic acid phosphatase (PAP), in alkaline phosphatase, and deterioration in bone radiology were associated with clinical evidence of relapse; this occured despite persistently low levels of plasma testosterone. Serum thyroxine, cortisol, and prolactin levels remained unchanged following orchiectomy or chronic administration of HOE 766. Practically all patients complained of hot flashes and experienced a decrease in libido and potency, but none developed gynecomastia or thromboembolic episodes. The data indicate that HOE 766 can be used safely as an alternative to castration or estrogens for the treatment of patients with androgen-dependent prostatic cancer.     

A study on transfer of ceftizoxime into prostatic and vesical tissues

Prostatic and vesical tissue levels of Ceftizoxime (CZX) were determined in 21 patients with prostatic hyperplasia after the intravenous administration of 1 g of CZX. Serum concentration on prostatic surgery continued to be 1.3 fold higher than that of healthy adults. Prostatic tissue levels attained a peak of 40.7 +/- 1.6 micrograms/g (mean +/- SE) at 30 minutes after administration and vesical tissue levels attained a peak of 72.4 +/- 24.8 micrograms/g at 30 minutes. The mean value was 21.0 +/- 6.4 micrograms/g in prostatic tissue after administration for 120 minutes with the tissue/serum ratio of 0.91. Prostatic tissue level in glandular dominant were slightly higher than those of myoglandular hyperplasia (P less than 0.1). Judging from its favorable transfer into the prostatic tissue and MIC against clinically isolated E. coli, Proteus sp. and Klebsiella, CZX seemed to be clinically useful in the treatment of prostatic infection.     

Na(+)/H(+) exchanger inhibitor HOE642 offers myoprotection in senescent myocardium independent of ischemic preconditioning mechanisms

BACKGROUND: Inhibition of Na(+)/H(+) exchange has been shown to provide functional protection during ischemia and reperfusion in mature heart. This study was undertaken to elucidate the effect of Na(+)/H(+) exchange inhibitor HOE642 in the aged rabbit heart. METHODS: Isolated rabbit hearts were subjected to 1 h of left descending coronary artery (LAD) ischemia and 1 h of reperfusion. To determine the effects of HOE642 on ischemia/reperfusion injury, seven aged or mature hearts received the Na(+)/H(+) exchange inhibitor HOE642 (1 microM) for 15 min before the ischemia and for 30 min after reperfusion. Seven aged (more than 135 weeks) or mature (15-20 weeks) rabbit hearts served as a control (untreated) with no interventions. Left ventricular pressures, monophasic action potentials and coronary flows were measured throughout the experiment and infarct size was detected at the end of experiment. RESULTS: (1) In the mature hearts, HOE642 improved postischemic functional recovery (63.1 +/- 5.0% vs. 84.4 +/- 5.4%, mature untreated vs. mature HOE, p < 0.05) and reduced infarct size as compared to untreated hearts (42.0 +/- 2.5% vs. 24.8 +/- 2.3%, mature untreated vs. mature HOE, p < 0.05). (2) Although infarct size in aged untreated hearts was significantly decreased as compared to mature untreated hearts (42.0 +/- 2.5% vs. 19.3 +/- 1.6%, mature untreated vs. aged untreated, p < 0.05), there are no significant differences regarding postischemic functional recovery between mature and aged untreated hearts (63.1 +/- 5.0% vs. 59.5 +/- 5.9%, mature untreated vs. aged untreated, p = n.s.). (3) In the aged hearts, HOE642 improved postischemic functional recovery as compared to untreated hearts (59.5 +/- 5.9% vs. 85.9 +/- 8.1%, aged untreated vs. aged HOE, p < 0.05). CONCLUSION: Na(+)/H(+) exchange inhibitor HOE642 is effective against ischemia-reperfusion injury in senescent as well as mature hearts.     

Effects of a potent LHRH-agonist on the pituitary gonadal axis with and without testosterone substitution

Summary In this study we investigated the effect of low and high dosages of a potent LHRH agonist on the pituitarygonadal axis with special consideration to the effect on the tubular compartment of the testis. Included were 3 treatment groups: the probands in Group I were treated with 3 x 50g HOE 766/week intranasally for 5 months; in Group II with 3 x 100 g HOE 766 intranasally/day for 6 months and in Group III with 3x200g HOE 766 intranasally plus 5mg fluoxymesterone orally/day for 5 months. With the low dose (Group I) no changes in the seminal parameters measured could be observed whereas LH and FSH levels increased in plasma, testosterone showed no change compared to preatreatment values. When high dosages/day of a potent LHRH agonist were administered without androgen replacement (Group II) pronounced decrease of LH and FSH took place, the testosterone plasma levels approached the female range. Spermatogenesis was arrested. The agonist plus androgen replacement (Group III) counteracted the suppression of spermatogenesis.     

Treatment with artificial beta-cell decreases very-low-density lipoprotein triglyceride synthesis in type I diabetes

The effect of restoration of euglycemia with the artificial beta-cell (Biostator GCIIS) on triglyceride metabolism was studied in seven normolipidemic patients with type I diabetes mellitus. Very-low-density lipoprotein triglyceride (VLDL-TG) transport was determined with [3H]glycerol as an endogenous precursor of VLDL-TG; the resultant kinetic data were evaluated by multicompartmental analysis. Studies of triglyceride metabolism were performed in diabetic patients taking their usual dose of subcutaneous insulin (control study) and after 72 h of euglycemia with the artificial beta-cell (Biostator study). Treatment with the artificial beta-cell resulted in a decrease in mean (+/- SE) 24-h plasma glucose levels from 199 +/- 9 to 123 +/- 7 mg/dl and an increase in mean plasma free-insulin levels from 12.3 +/- 1.9 to 27.6 +/- 4.2 microU/ml (P less than .05). These changes were accompanied by a decrease in mean plasma TG levels from 134 +/- 29 to 88 +/- 15 mg/dl (P less than .05). Kinetic studies demonstrated that the change in plasma triglyceride levels was primarily due to a decrease in VLDL-TG transport (i.e., synthesis), which fell from 11.7 +/- 2.5 mg X h-1 X kg-1 ideal wt during the control study to 7.5 +/- 2.0 mg X h-1 X kg-1 ideal wt during the Biostator study (P less than .05). There was no significant change in fractional catabolic rates of VLDL-TG between the two studies (0.35 +/- .05 vs. 0.38 +/- .07 h-1).(ABSTRACT TRUNCATED AT 250 WORDS)     

The neuromuscular response of infants to a continuous infusion of succinylcholine

The response of the adductor of the thumb to ulnar nerve stimulation (0.1 Hz) was evaluated during continuous infusion of succinylcholine (SCh) in 20 infants anesthetized with halothane (1%) and N2O2/O2. Train-of-four stimulation (2 Hz for 2 s) was used to differentiate between phase I and phase II block. Some infants were very resistant to the neuromuscular effects of SCh. These infants (Group 1) were younger in age, 57 +/- 15 days (mean +/- SE) and required 24.6 +/- 3.3 mg X kg-1h-1 SCh to achieve more than 90% depression of the twitch. Older infants (Group 2), 188 +/- 33 days, required significantly less (P less than 0.001) SCh (8.7 +/- 0.5 mg X kg-1h-1) to achieve the same degree of twitch suppression. Group 1 infants recovered from the effects of SCh very rapidly. After 10 mg/kg SCh, the train-of-four ratio in Group 1 infants recovered to 75% in 4.7 +/- 0.6 min, whereas it took 34 +/- 10 min in Group 2 infants (P less than 0.01). Tachyphylaxis developed in infants after 3.6 +/- 0.3 mg/kg (mean +/- SE) and phase II block after 5.3 +/- 0.7 mg/kg (P less than 0.05) SCh. Combining the data of infants with that of children from a previous study conducted in a similar fashion resulted in significant correlation (P less than 0.001) between the log age and SCh requirement. The rate of administration of a continuous infusion of SCh in infants should be based upon the response of infants and not on a fixed dose (mg X kg-1 X h-1).     

Long-term myocardial preservation: beneficial and additive effects of polarized arrest (Na+-channel blockade), Na+/H+-exchange inhibition, and Na+/K+/2Cl- -cotransport inhibition combined with calcium desensitization

BACKGROUND: Polarized arrest, induced by tetrodotoxin (TTX) at an optimal concentration of 22 micromol/L, has been shown to reduce ionic imbalance and improve myocardial preservation compared with hyperkalemic (depolarized) arrest. Additional pharmacologic manipulation of ionic changes (involving inhibition of Na+ influx by the Na+/H+ exchanger [HOE694] and Na+/K+/2Cl- cotransporter [furosemide], and calcium desensitization [BDM]) may further improve long-term preservation. In this study, we (i) established optimal concentrations of each drug, (ii) determined additive effects of optimal concentrations of each drug and (iii) compared our optimal preservation solution to an established depolarizing cardioplegia (St Thomas' Hospital solution No 2: STH2) used during long-term hypothermic storage for clinical transplantation. METHODS: The isolated working rat heart, perfused with Krebs Henseleit (KH) buffer was used; cardiac function was measured after 20 min aerobic working mode perfusion. The hearts (n=6/group) were arrested with a 2 ml infusion (for 30 sec) of the polarizing (control) solution (22 micromol/L TTX in KH) or control+drug and subjected to 5 hr or 8 hr of storage at 7.5 degrees C in the arresting solution. Postischemic function during reperfusion was measured (expressed as percentage of preischemic function). RESULTS: Dose-response studies established optimal concentrations of HOE694 (10 micromol/L), furosemide (1.0 micromol/L) and BDM (30 mmol/L) in the polarizing (control) solution. Sequential addition to the control solution (Group I) of optimal concentrations of HOE694 (Group II), furosemide (Group III), and BDM (Group IV) were compared with STH2 (Group V); postischemic recovery of aortic flow was 29+/-7%, 49+/-6%*, 56+/-2%*, 76+/-3%*, and 25+/-6%, respectively (*P<0.05 vs. I and V). Creatine kinase leakage was lowest, and myocardial ATP content was highest in Group IV. CONCLUSIONS: A polarizing preservation solution (KH+TTX) containing HOE694, furosemide, and BDM significantly enhanced long-term preservation compared with an optimized depolarizing solution (STH2) used clinically for long-term donor heart preservation.     

Nuclear magnetic resonance in advanced prostate cancer (stage D)

Nuclear Magnetic Resonance (NMR), a recently developed diagnostic method, has proved to be useful in the study of patients with prostatic disease. The authors report their experience with this technique in 10 cases of advanced prostate cancer (stage D) treated with LH-RH agonists (HOE 766-Buserelin). NMR provided information on the size of the prostate, the invasion of the vesical floor and seminal vesicles and the involvement of the pelvic and retroperitoneal nodes. It was also useful for ruling out metastases in the pelvis and spinal column, and showed an excellent correlation with the bone scan. In 2 untreated cases, NMR was sufficient by itself to diagnose metastatic prostate cancer. However, given the current lack of experience, it is not yet possible to draw conclusions concerning the superiority of this technique over other methods in the diagnosis and staging of prostatic carcinoma.     

A 12-month clinical study of LA-2585 (45.0 mg): a new 6-month subcutaneous delivery system for leuprolide acetate for the treatment of prostate cancer

PURPOSE: The safety, efficacy and pharmacokinetics of LA-2585, a new 6-month subcutaneous depot of leuprolide acetate (Atrix Laboratories, Fort Collins, Colorado) were investigated in patients with prostate cancer. MATERIALS AND METHODS: In this 12-month, open label, multicenter study 111 patients with adenocarcinoma of the prostate were administered 45.0 mg LA-2585 subcutaneously once every 6 months. The primary efficacy parameter was serum testosterone 50 ng/dl or less. Leuprolide acetate pharmacokinetics were analyzed in a subset of 28 patients. RESULTS: Of the 111 enrolled patients 103 (93%) completed the 12-month study. Eight patients withdrew due to nonmedical reasons in 1, disease progression in 5 and cardiovascular disease in 2. By day 28, 108 of the 109 remaining patients (99%) achieved testosterone suppression, while 1 who never attained suppression was withdrawn at day 85. Mean time to castrate suppression was 21.2 days (median 21). At study completion 102 of 103 patients (99%) were below medical castrate testosterone levels of 50 ng/dl (mean +/- SE 12.3 +/- 2.1 ng/dl) with 91 of 103 (88%) at less than 20 ng/dl. Mean luteinizing hormone decreased from 6.98 +/- 0.48 mIU/ml at baseline to 0.23 +/- 0.14 mIU/ml at month 12. Luteinizing hormone was consistently below 1 mIU/ml. Mean prostate specific antigen decreased 97% from 39.8 +/- 21.5 ng/ml at baseline to 1.2 +/- 0.3 ng/ml at 12 months. No clinically significant flare reactions were observed. The most common treatment related adverse event was mild to moderate hot flashes. CONCLUSIONS: LA-2585 (45.0 mg depot) consistently produced and maintained safe and effective serum testosterone suppression with total serum testosterone well below the medical castrate level of less than 50 ng/dl.     

Synergistic effect of coumadin and cytoxan in reducing lung metastases

Lung metastasis is a frequent cancer complication resulting in significant mortality. This study evaluates the effect of coumadin and cytoxan alone and in combination on lung metastases in rats challenged with Morris hepatoma 3924A. Seventy-seven male American Cancer Institute (ACI) rats weighing 200 g were studied. Thirty-seven rats received coumadin orally for six days, which resulted in a prothrombin time 2 times that of controls (30 sec). All rats received 1 X 10(5) clumped Morris hepatoma cells via tail vein injection. Animals were divided into four groups: Group I (controls, n = 20) received no antitumor treatment; group II rats (n = 20) received 25 mg/kg cytoxan intraperitoneally at the time of tumor challenge; group III animals (n = 19) received coumadin alone; while group IV (n = 18) received both coumadin and cytoxan. Rats were evaluated for number of lung metastases and lung weight at 3 weeks postinjection. Data was subjected to statistical analysis by the Student's test. The mean number of lung metastases were 580 +/- 45 in group I, 350 +/- 310 in group II, 330 +/- 263 in group III, and 200 +/- 161 in group IV (P less than .005 [IV] v [I], P less than .05 [IV] v [II], [III]), (P less than .05 [II] v [I]), (P less than .05 [III] v [I]). Mean lung weights were 2.597 g +/- 1.65 in group I, 2.049 g +/- 0.75 in group II, 1.898 g +/- 0.80 in group III, and 1,677 g +/- 0.31 in group IV. (P less than .025 [IV] v [I], P less than .05 [IV] v [II]).(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of microvessel densities in rat prostate tissues treated with finasteride, bicalutamide and surgical castration: A preliminary study

BACKGROUND: A group of anti-androgens with different mechanisms of action and adverse effects have been investigated in patients with gross hematuria related to benign prostate hyperplasia; however, there is not yet any consensus about the standard management of these patients. The present study aims to identify if any one type of the hormonal intervention is superior in terms of the suppression of microvessel formation in the prostate. MATERIALS AND METHODS: A total of 28 mature, healthy male Sprague-Dawley rats (300 +/- 50 g) were used in this study. The rats were randomly assigned to one of four groups (n = 7 per group). The effects of three different hormonal therapies on angiogenesis and microvascularity in rat ventral prostate were compared. Groups 1 and 2 were treated for 28 days with finasteride and bicalutamide, respectively, and rats from Group 3 underwent surgical castration. Following treatment, all rats included in the study underwent dissection of the ventral prostate and immunohistochemical analysis of microvessel density by factor VIII-related antigen. RESULTS: The mean number of microvessels in the finasteride and bicalutamide groups was 24.5 (+/-8.44 SE) and 27 (+/-9.89 SE) respectively. In contrast, the castration and control groups had microvessel numbers of 12.9 (+/-5.35 SE) and 40.3 (+/-5.03 SE) respectively. Differences were statistically significant between all three treatment groups and the controls (P < 0.005); the number of microvessels in rat prostate tissues of the control group was significantly higher than the treatment groups. Mean microvessel densities in the bicalutamide and finasteride groups were significantly higher than microvessel densities in the castration group (P < 0.005). There was no statistically significant difference between mean microvessel number in rat prostate tissue treated with finasteride or bicalutamide (P > 0.05). CONCLUSIONS: Even though finasteride was not as effective as castration in reducing microvessel number, its effect was equal to that of bicalutamide in terms of suppressing the angiogenesis in prostatic tissue. Based on the findings of the present study, finasteride might offer a viable option in the management of macroscopic hematuria by inhibition of microvessel formation within the prostatic tissue. Further clinical studies are warranted.     

The pulmonary effects of opiate blockade in septic shock

Sepsis remains the most common associated factor in acute respiratory failure (ARF). Endogenous opiates are known to have both respiratory and cardiovascular depressant effects. Because there is a high level of circulating endogenous opiates in sepsis, the possible role of opioids in the ARF syndrome seen in sepsis was studied. Sixteen piglets were infused with an LD100 dose (7.5 X 10(10) organisms/kg) of live Escherichia coli (Type 09-41). The pigs were hemodynamically monitored. Serial blood samples were taken for arterial blood gases and lactate. Serial lung biopsies were taken for determining wet/dry lung weight ratios and for histology. Group I (n = 8): septic shock controls without naloxone; group II (n = 8): naloxone treated, given as 2 mg/kg/hr intravenous boluses, starting within 1 min of E. coli infusion. All animals died of septic shock. Survivors at 150 min in group II had a higher blood pressure than group I (67.7 +/- 5.33 SEM vs 39.0 +/- 9.39) and cardiac output was also greater (1.07 +/- 0.23 vs 0.25 +/- 0.25). By 210 min, group I had no survivors (0/8) while 3/8 in group II survived. Pulmonary vascular resistance in group II at 90 and 120 min (870.8 +/- 274.1 and 942.5 +/- 12.9, respectively) was lower than in group I (2868.3 +/- 843.6 and 4156 +/- 1067). The PO2 was markedly better in group II and at 90 min; controls had a PO2 70.7 +/- 13.0, while group II had a PO2 111.4 +/- 8.4 (P less than 0.05). PCO2 levels showed a progressive rise in group I from 39.25 +/- 1.4 to 49.4 +/- 8.57.(ABSTRACT TRUNCATED AT 250 WORDS)     

Transplantation of purified single-donor canine islet allografts with cyclosporine

We evaluated the survival of highly purified freshly isolated pancreatic islets transplanted from single canine donors into 20 outbred mongrel dogs immunosuppressed with cyclosporine or untreated. The grafts (mean weight +/- SE, 0.5 +/- 0.1 g, containing 122 +/- 8 X 10(3) islets; purity 91% by electron microscopy) were transplanted into 3 groups of dogs: group 1, autograft without CsA (5444 +/- 688 islets/kg body weight, n = 6); group 2, allograft without CsA (6669 +/- 1744, n = 4); and group 3, allograft with CsA (8645 +/- 1149, n = 10). The CsA was injected i.m. daily for 4 days before and 30 days after transplantation. Fasting plasma glucose (PG, mg/dl) and serum CsA trough values were determined daily. Intravenous glucose tolerance tests were done before and after transplantation, for calculation of K values (decline in glucose, %/min; preoperatively, mean K = 3.9 +/- 0.2). In group 1 all 6 dogs were normoglycemic (PG = 98 +/- 2 and K = 1.8 +/- 0.2) at 1 month; in group 2 the graft failed in all 4 dogs, at 4 +/- 1.2 days; in group 3 all 10 dogs were normoglycemic initially. Of the group 3 dogs, 4 died (intussusception developed in 2, and the graft failed at 3 and 9 days in 2 the CsA values of which were less than 300 micrograms/L preoperatively), but the other 6 were still normoglycemic when the CsA was stopped at 30 days (mean PG = 132 +/- 16 and K = 0.9 +/- 0.2; P less than 0.05 vs. group 1). Their CsA values were 708 +/- 197 before and 359 +/- 41 micrograms/L during the third week after transplantation; their grafts failed 12.3 +/- 3.4 days after the cessation of CsA. This data is unique in demonstrating prolonged function of purified allogeneic islets transplanted from individual outbred canine donors, but glucose tolerance was impaired. CsA at serum levels greater than 300 micrograms/L induced prolonged survival of purified canine islets and rejection was prompt when it was stopped.     

Trabecular architecture in women and men of similar bone mass with and without vertebral fracture: II. Three-dimensional histology

We recently developed a simple and inexpensive method that complements established bone histomorphometry procedures by enabling the two-dimensional imaging of cancellous bone to be viewed within its three-dimensional context with the marrow tissue in place and without detriment to the material for other histological purposes. The method, based on the preparation and superficial staining of slices 300 microm thick, enables "real" (i.e., unstained) trabecular termini to be separated from "artifactual" (i.e., stained) termini, providing a direct measure of cancellous connectivity in osteopenic bone. The technique was applied to osteopenic age-matched, white, postmenopausal women (31 with and 22 without vertebral compression fractures) with a similar bone status, as measured at the spine by absorptiometry and at the iliac crest by histology (see part I of this study). Despite the similarity in the mass of trabecular bone at either site, the results showed a significant difference (p < 0. 05) in the number of "real" trabecular termini between the groups, such that the fracture group had almost four times as many termini (mean +/- SE: 1.98 +/- 0.51/30 mm(2)) at the iliac crest as the nonfracture group (mean +/- SE: 0.53 +/- 0.31/30 mm(2)). Previous histomorphometry of the same material failed to detect a structural distinction between the two groups using established variables. It was concluded that a mass-independent trabecular discontinuity contributes to skeletal failure and that determination of the number of "real" disconnections (i.e., unstained termini) by the direct method proposed may provide a more sensitive discriminant of fracture than the present indirect procedures. A group of fracture and nonfracture men (see part I) suggested a similar distinction (fracture: 0.69 +/- 0.30/30 mm(2); nonfracture: 0.18 +/- 0.18/30 mm(2)), although the difference was not significant.     

"Defasciculation" with metocurine prevents succinylcholine-induced increases in intracranial pressure

In order to determine whether a small, "defasciculating" dose of metocurine could prevent increases in intracranial pressure (ICP) induced by succinylcholine (Sch), the authors studied 12 patients (ages 25-79 yr) undergoing craniotomy for excision of malignant supratentorial gliomas. After insertion of a subarachnoid bolt for ICP monitoring and a radial arterial cannula for determination of blood pressure and blood gas tensions, six patients (group I) were randomly allocated to receive MTC 0.03 mg/kg 3 min before induction of general anesthesia with thiopental 4 mg/kg and nitrous oxide 70% in O2. Six other patients (group II) received saline 0.015 ml/kg instead of MTC, followed by the same induction sequence. After induction of anesthesia, ventilation was controlled by mask (PaCO2 = 40 mmHg +/- 2 SE), and arterial and intracranial pressures were allowed to stabilize. Four minutes after thiopental administration (7 min after MTC), after a 1-min period of relatively stable arterial pressure and ICP, Sch 1 mg/kg was administered as a bolus. ICP and blood pressure were recorded continuously until normal twitch tension was restored. In group I (MTC pretreatment), ICP did not change significantly from the mean value observed before Sch, 14 mmHg +/- 2 SE. In group II (saline pretreatment), ICP increased from 11 mmHg +/- 2 SE to 23 mmHg +/- 4 SE (P less than .05). This study not only confirms previous work showing that Sch may induce marked ICP increases in lightly anesthetized patients with intracranial mass lesions, but also indicates that pretreatment with a "defasciculating" dose of MTC can prevent these potentially deleterious ICP increases in patients known to be at risk.     

Hypergastrinemia in children with duodenal ulcer

Serum gastrin concentrations were determined in 25 children with duodenal ulcer (DU) and 25 normal children. Fasting values were significantly higher in DU children (mean +/- SE = 60.4 +/- 9.7 pg/mL) than in controls (mean +/- SE = 38.0 +/- 4.2 pg/mL; P less than .05). Integrated gastrin response to meal stimulation was also significantly higher in DU children (mean +/- SE = 140.5 +/- 32.4%) than in controls (mean +/- SE = 62.3 +/- 12.2%; P less than .05). Excessive gastrin activity (greater than normal mean + 2 SD), either fasting or meal-stimulated, occurred in 11 of 17 normal acid secretors and in two of eight hypersecretors in the DU group. The present findings suggest that excessive gastrin activity is a major factor in the pathogenesis of childhood DU. Unlike adult DU, which is associated with normal fasting gastrin concentrations, childhood DU manifests exaggerated gastrin activity both in the fasting and postprandial states.     

Myocardial protective effect of hypothermia during extracorporeal circulation -- by quantitative measurement of myocardial oxygen consumption -.

OBJECTIVE: To evaluate the effect of systemic temperature on myocardial protection during extracorporeal circulation, we quantitatively evaluated the relationship between myocardial oxygen consumption and rectal temperature. MATERIALS AND METHODS: Myocardial oxygen consumption during cardiac arrest was calculated via blood gas analysis of venous blood samples collected from the coronary sinus. The rectal temperatures of the patients during extracorporeal circulation ranged from 16.0 degrees C to 33.5 degrees C. The patients were classified into three groups according to their rectal temperature: group I (n=10; rectal temperature: 20.3+/-1.80 degrees C), group II (n=24; rectal temperature: 29.4+/-0.97 degrees C), and group III (n=29; rectal temperature: 31.7+/-0.72 degrees C). The myocardial oxygen consumption of each group was then compared. RESULTS: The average of the myocardial oxygen consumption of all cases was 62.5+/-64.0 O(2) ml/min/100 mm(3) left ventricle volume, and the averages of the individual groups were 26.9+/-28.8 in group I, 72.2+/-71.8 in group II, and 69.3+/-62.6 in group III. There was a significant difference in the oxygen consumption between group I and the other two groups. There was a positive correlation between the rectal temperature and myocardial oxygen consumption, as reflected in the following formula: Y=-0.3 x X +1.10 x X(2)-0.02 x X(3) (Y, myocardial oxygen consumption; X, rectal temperature; R(2)=0.533; P<0.0001). CONCLUSION: This study suggested that rectal temperature below 22.5 degrees C is advantageous due to the resultant myocardial protection such hypothermia affords.     

A study of plasma proteins in the sol phase of sputum from patients with chronic bronchitis.

We have studied the sputum/serum protein concentration ratios from 23 patients with bronchitis both in the stable clinical state and during acute chest infections. During the stable state there was a significant negative correlation (2 P less than 0.005) between the ratio and protein size. The ratios of IgG, IgA, C3, and alpha 1-antichymotrypsin were significantly displaced from this relation suggesting local production in the lung. IgM was found in all samples and alpha 2-macroglobulin in 55% of non-infected samples which may be the result of local production rather than transudation from serum, because of their larger size. During acute chest infections the albumin content of sputum rose from a mean sputum/serum ratio of 0.83 (SE +/- 0.08) X 10(-2) to 13.77 (SE +/- 3.21 X 10(-2) suggesting increased transudation from the blood. In the presence of increased transudation, local production of protein appears to be less significant.     

Recovery after anesthesia with propofol in otorhinolaryngologic surgery of brief duration

This study was designed to assess recovery from total intravenous anaesthesia with propofol for short ENT procedures. Twenty-six patients (ASA I and II) were assigned to two groups of thirteen: one breathed air (Laser laryngeal microsurgery), the second N2O-O2 (FIO2 : 0.5) (various ENT procedures). The induction sequence was exactly the same for both groups: oral premedication with 10 mg diazepam one hour before surgery, I mg pancuronium bromide, 2 micrograms X kg-1 fentanyl, denitrogenation within 3 min, after which propofol was delivered (2.5 mg X kg-1). When the eye-lash reflex had disappeared (time recorded), 1.5 mg X kg-1 suxamethonium was given and laryngotracheal intubation carried out. A continuous infusion of propofol (9 mg X kg-1 X h-1) was started. Surgery began 5 +/- 2 min after the start of propofol infusion. The durations of anaesthesia, surgery and propofol infusion were similar in both groups. To have good surgical conditions, it was necessary to give repeated doses of propofol for 15 patients. Thus, the total dose of propofol was significatively different between the two groups: 24.5 +/- 6.7 mg X kg-1 X h-1 in group "air" versus 16 +/- 3.6 mg X kg-1 X h-1 in group "N2O-O2" (p less than 0.001). Extubation occurred within 16 +/- 8 min in group "air", being more rapid in group "N2O-O2" (11 +/- 9 min; no significant difference). Recovery was assessed with two psychomotor tests: choice reaction time (CRT) and tracing test (TT).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of glyburide on glycemic control, insulin requirement, and glucose metabolism in insulin-treated diabetic patients

Glycemic control and glucose metabolism were examined in 5 patients with insulin-dependent diabetes mellitus (IDDM) and 8 insulin-treated non-insulin-dependent diabetes mellitus (NIDDM) patients before and after 2 mo of therapy with glyburide (20 mg/day). Glycemic control was assessed by daily insulin requirement, 24-h plasma glucose profile, glucosuria, and glycosylated hemoglobin. Insulin secretion was evaluated by glucagon stimulation of C-peptide secretion, and insulin sensitivity was determined by a two-step euglycemic insulin clamp (1 and 10 mU X kg-1. X min-1) performed with indirect calorimetry and [3-3H]glucose. In the IDDM patients, the addition of glyburide produced no change in daily insulin dose (54 +/- 8 vs. 53 +/- 7 U/day), mean 24-h glucose level (177 +/- 20 vs. 174 +/- 29 mg/dl), glucosuria (20 +/- 6 vs. 35 +/- 12 g/day) or glycosylated hemoglobin (10.1 +/- 1.0 vs. 9.5 +/- 0.7%). Furthermore, there was no improvement in basal hepatic glucose production (2.1 +/- 0.2 vs. 2.4 +/- 0.1 mg X kg-1 X min-1), suppression of hepatic glucose production by low- and high-dose insulin infusion, or in any measure of total, oxidative, or nonoxidative glucose metabolism in the basal state or during insulin infusion. C-peptide levels were undetectable (less than 0.01 pmol/ml) in the basal state and after glucagon infusion and remained undetectable after glyburide therapy. In contrast to the IDDM patients, the insulin-treated NIDDM subjects exhibited significant reductions in daily insulin requirement (72 +/- 6 vs. 58 +/- 9 U/day), mean 24-h plasma glucose concentration (153 +/- 10 vs. 131 +/- 5 mg/dl), glucosuria (14 +/- 5 vs. 4 +/- 1 g/day), and glycosylated hemoglobin (10.3 +/- 0.7 vs. 8.0 +/- 0.4%) after glyburide treatment (all P less than or equal to .05). However, there was no change in basal hepatic glucose production (1.7 +/- 0.1 vs. 1.7 +/- 0.1 mg X kg-1 X min-1), suppression of hepatic glucose production by insulin, or insulin sensitivity during the two-step insulin-clamp study. Both basal (0.14 +/- 0.05 vs. 0.32 +/- 0.05 pmol/ml, P less than .05) and glucagon-stimulated (0.24 +/- 0.07 vs. 0.44 +/- 0.09 pmol/ml) C-peptide levels rose after 2 mo of glyburide therapy and both were correlated with the decrease in insulin requirement (basal: r = .65, P = .08; glucagon stimulated: r = .93, P less than .001).(ABSTRACT TRUNCATED AT 400 WORDS)