TREATMENT OF DIABETIC PATIENTS—Observations on the Use of Carbutamide and Tolbutamide

Of a group of 32 patients with diabetes, 26 had a favorable modification of the disease in response to administration of butyl-sulfonyl-urea. All but one of the patients who had good response were past the age of 38. All diabetic patients included in this group were those with little or no tendency to ketosis after cessation of insulin administration. No toxic manifestations were noted except for a slight decrease in leukocytes in one case.     

Insulin hypoglycemia test and releasing hormone (corticotropin-releasing hormone and growth hormone-releasing hormone) stimulation in patients with pituitary failure of different origin

To investigate the efficacy of endocrine evaluation in diagnosing and localizing the cause of anterior pituitary failure, 17 patients with suprasellar space-occupying lesions, 4 patients with intrasellar tumors, 8 patients with no detectable anatomical lesion, 1 patient with posttraumatic failure and 1 patient with septooptical dysplasia were investigated. Endocrine evaluation consisted of measuring adrenocorticotropic hormone (ACTH), cortisol, and growth hormone (GH) levels during insulin hypoglycemia test (IHT) and after administration of corticotropin-releasing hormone (CRH) and growth hormone-releasing hormone (GRH). In addition, basal prolactin levels, gonadal and thyroid function were evaluated. The results showed that 4 of 17 patients with suprasellar tumors had normal ACTH and GH responses during IHT and after releasing hormone (RH) administration. Five of these patients had a normal ACTH or cortisol rise but no GH response during IHT. All 5 had a normal ACTH and 3 had normal GH rise after RH. Seven patients with suprasellar tumors had no ACTH or GH response during IHT, but all had an ACTH response to CRH. Only 3 of this group had a GH response to GRH. There was one exception of a patient who showed a GH and ACTH rise during IHT but only a blunted ACTH and no GH rise after RH administration. Four patients with pituitary failure and no demonstrable lesion had an ACTH rise after CRH but no GH rise after GRH, whereas in 3 patients with isolated ACTH deficiency no ACTH rise after CRH was seen. In 4 patients with nonsecreting pituitary tumors normal ACTH responses to IHT and CRH were seen, whereas GH rose during IHT only in 1 patient.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum alpha-subunit elevation after TRH administration: a valuable test in presurgical diagnosis of gonadotropinoma?

OBJECTIVES: Clinically nonfunctioning pituitary adenomas (CNFPAs) represent about 30% of pituitary macroadenomas, gonadotropinomas being the most frequent among them. The aim of the present study is to re-evaluate the usefulness of the measurement of alpha-SU serum level in response to TRH stimulation in detecting the gonadotropic nature of nonfunctioning pituitary adenomas before the neurosurgical treatment. MATERIAL AND METHODS: We have studied 14 patients with CNFPAs. The response of alpha-SU to the administration of TRH was studied in each patient before the surgery. alpha-SU blood serum level increase over 50% of the baseline level after TRH treatment was considered to be significant. RESULTS: The patients were divided into 2 groups, each including 7 subjects. The first group included the patients with gonadotropinomas (tumors immunopositive for FSH and/or LH or their free subunits). The second group included the patients with adenomas immunonegative for gonadotropins and alpha-SU. The basal level of alpha-SU was elevated over the upper limit of normal range in two patients of the first group (gonadotroph adenomas) and in one in the second group. All but one patient from the first group and none of seven patients with tumors immunonegative for FSH, LH or alpha-SU, had a significant alpha-SU (over 50%) response to TRH. In three of seven patients with gonadotropins immunonegative tumors a decrease of alpha-SU serum level after TRH was observed. CONCLUSION: The measurement of alpha-SU serum level in response to TRH administration seems to be useful in preoperative identification of gonadotroph adenomas among other nonfunctioning pituitary adenomas.     

Oxidative status in chronic hepatitis C: the influence of antiviral therapy and prognostic value of serum hydroperoxide assay

The effect of alpha-interferon (alpha-IFN) and ribavirin (RBV) treatment on oxidative status in chronic hepatitis C (CHC) is unknown. AIM: To study the time course of oxidative status in patients with CHC during alpha-IFN and RBV administration, and to evaluate the role of oxidative status in order to predict the therapeutic response. PATIENTS AND METHODS: Fifty one patients with CHC were studied. All received a combination of alpha-IFN and RBV for 6 or 12 months in relation to the type of response. The hydroperoxides concentration in serum test samples by D-ROM test was measured in all of the patients before therapy. In 27 patients, hydroperoxides were also measured during the treatment and during the 12 subsequent months. RESULTS: Cross-sectional analysis demonstrates that patients with a successive long-term response had a lower basal serum hydroperoxide concentration than non-responders (280 +/- 40.8 vs 337 +/- 83 CARR Units, p < 0.05). This resulted to be an independent factor predictive of long-term response in the multi-varied analysis. Longitudinal observation on 27 patients showed that the mean hydroperoxide concentration decreased significantly during treatment (T0 329 +/- 79.2 vs T12 272 +/- 34.5 CARR Units) and that the decrease in the mean values was mainly due to variations in the relapsers group. CONCLUSIONS: Normal basal hydroperoxide concentration helps to predict long-term response to combination therapy. The D-ROM test may be used for screening patients before treatment.     

Endogenous opiate modulators of insulin secretion in the obese

The effects of endogenous opiates on insulin response to oral glucose load were studied in obese subjects and in lean healthy volunteers. None of these having a family diabetes. After 3 days on an 1,800 cal./m2, 40% carbohydrate diet all subjects underwent two standard 75 g oral glucose tolerance tests (OGTT), one of which was accompanied by an i. v. administration of 10 mg of, an antagonist of opiates, the naloxone. In one group of obese impaired oral glucose tolerance test occurred. All obese, but not the lean healthy volunteers, showed: 1) increased basal plasma insulin levels, 2) higher insulin response to OGTT, 3) a decrease in insulin response to OGTT after naloxone administration, with significant differences at 60 min (p less than 0.01) and 90 min (p less than 0.025). In none of the subjects significant differences were observed in blood glucose levels after OGTT plus naloxone administration. These data suggest that increased endogenous opiates may affect insulin response to glucose in obese with impaired or normal oral glucose tolerance test. At present there seems to be no satisfactory explanation for unchanged blood glucose levels during OGTT with and without naloxone despite a decrease in insulin secretion in the obese patients.     

艾司洛尔和右旋美托咪啶对减轻患者插管 和喉镜检查的拟交感反应分析

目的：比较艾司洛尔和右旋美托咪啶减弱神经外科患者插管和喉镜检查的拟交感反应的疗效。方法：选取在我院神经外科拟 接受选择性神经外科手术的90 例患者。患者平均随机分为三组。对照组：静注给予20 mL生理盐水;右旋美托咪啶组：1 ug/kg右 旋美托咪啶使用生理盐水稀释至20 mL静注;艾司洛尔组：1.5 mg/kg 艾司洛尔使用生理盐水稀释至20 mL静注。所有患者均接 受2 min 的麻醉诱导,所有药物均在10 min 内滴注完毕。在给药后、诱导后及气管插管后1、2、3、5、10、15 min 后对患者心率 （HR）、收缩压、舒张压、平均动脉压进行记录,同时记录患者基线值。结果：与对照组相比,右旋美托咪啶组插管后心率和血压未见 显著性差异;艾司洛尔组插管后1、2、3 min 后血压及插管后5 min 的心率显著上升。结论：对减弱神经外科患者插管和喉镜检查 的拟交感作用,右旋美托咪啶比艾司洛尔更为有效。     

Menstrual disturbances in chronic renal failure.

Twelve female patients undergoing intermittent hemodialysis (HD) and 5 females posttransplantation (PT) were studied. All the HD patients had menstrual disturbances and 5 had galactorrhea. The mean basal LH level was significantly elevated (p less than .05) in patients on HD compared to normal controls, but the mean LH response to luteinizing hormone releasing hormone (LRH) was not significantly different from the control group. Mean basal FSH and the FSH response to LRH was normal. In the PT pateints the LH response to LRH was significantly greater at 120 min when compared to normal females. In the HD group the serum 17B estradiol, progesterone and testosterone levels were significantly lower than in the controls but in the PT group only testosterone levels were significantly lower. These results differ from those previously found in uremic males. Elevated prolactin levels were found in the patients on hemodialysis and correlated well with the presence of galactorrhea. These was no correlation between the elevated prolactin levels and amenorrhea in the patients on hemodialysis but one PT patient with amenorrhea had elevated prolactin levels.     

Immunologic and clinical improvement of progressive coccidioidomycosis following administration of transfer factor

Three patients with progressive coccidioidomycosis were given preparations of transfer factor (TF). Adverse reactions to TF were minimal. Following TF administration two of these patients had prolonged clinical remissions in their coccidioidal disease. Cellular immune responses were sequentially evaluated by coccidioidininduced delayed-type skin tests, lymphocyte blast transformation and macrophage inhibition factor production (MIF). These three patients each exhibited different cellular immune patterns before and after TF administration. Two patients converted their coccidioidin skin tests, and one converted lymphocyte transformation response to coccidioidin. Also, TF apparently favorably affected the MIF response in all three patients.     

Familial ADH-responsive diabetes insipidus: response to thiazides and chlorpropamide

Twenty cases of familial ADH-responsive diabetes insipidus were identified within five generations, and eight patients were studied by one of two established dehydration protocols. In each case there was partial to total failure of response to the initial administration of ADH which was slowly corrected by continued administration. This initial failure can lead to misinterpretation of the dehydration test unless the medullary solute washout effect is taken into account in chronically polyuric patients.Treatment consisted of thiazides and/or chlorpropamide. All cases responded well.The response to chlorpropamide suggests that the failure of ADH production is not complete in these patients, and that the major defect is a failure of ADH release in response to normal stimuli. Chlorpropamide may act by either facilitating ADH release or by synergistically interacting with available ADH at the tubular level.     

Desensitization at the first stage of IGE-mediated response as hay fever prophylaxis

The aim of our work was to assess the prophylactic aspects of desensitization at the first stage of IgE-mediated response to grass pollen antigens (GPA). Forty six patients aged 10-45 (Me = 20.45) years (group I) and 50 patients aged 11-45 (Me = 19.17) years (group II) were included in to the study. All of them: 1) suffered from allergic rhinitis due to house dust (HD), feathers (F), weed (W) or tree (T) pollen, 2) had also some other allergic diseases, 3) had positive family history of allergic disorders, 4) had reproducible, strongly positive skin reaction of type I to GPA, but 5) did not show any clinical symptoms of hypersensitivity to GPA. Specific immunotherapy with HD, F, W, and T aqueous extracts was administered to both groups for at least 3 successive years, while parallel desensitization with GPA aqueous extract was carried out in group I, only. The symptoms of grass pollinosis were searcher for and the effects of immunotherapy were evaluated in all the patients over the period of at least 5 successive years after the complete course of vaccines administration. Clinical signs of hypersensitivity to GPA became evident in 6 patients (13.04%) of group I and in 27 patients (54.00%) of group II (p less than 0.001). Thus the desensitization at the first stage of IgE-mediated response to GPA effectively prevented development of the symptomatic hay fever. However, the disease revealed itself in few cases still much later and its course was much milder than in people who were not subjected to such a preventive desensitization.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dissociated response of thyrotropin and prolactin to dopamine receptor blockade with domperidone in hypothyroid subjects.

To investigate the hypothesis of an altered hypothalamic dopaminergic activity in primary hypothyroidism, eight patients with hypothyroidism and seven normal subjects, all female, were studied. All of them were submitted to two tests: TRH stimulation and after the administration of dopamine receptor-blocking drug, Domperidone. The hypothyroid patients with basal TSH values less than or equal to 60 mU/L (4 cases--group 1) had lower PRL levels than the remaining 4 subjects with TSH greater than 60 mU/L (group 2) (p less than 0.001), despite all patients presenting the PRL levels within the normal range. A significant increase occurred for both TSH and PRL after the administration of TRH and Domperidone in normal as well as in the hypothyroid subjects, except for TSH in group 1 after the administration of Domperidone. The area under the curve for PRL response to THR was not different between the normal subjects and both hypothyroid groups, while that under the curve for TSH was greater in the hypothyroidism as a whole than in the normal subjects (p = 0.006) and between the hypothyroid groups, being greater in group 2 than in 1 (p less than 0.009). In relation to Domperidone, the area under the curve for TSH was significantly higher in group 2 when compared to the normal controls (p less than 0.001), while for PRL it was not different between hypothyroid groups in relation to normal controls and when groups I and II were compared. These results suggest that the hypothalamic dopamine activity is not altered in primary hypothyroidism and favor the small relevance of dopamine on the control of TSH secretion.     

Chronic treatment of Paget's disease of bone with synthetic human calcitonin.

Twelve patients with Paget''s disease of bone were treated with synthetic human calcitonin for seven to 26 months (mean 15.3 months). This group included six patients who had previous therapy. Eleven of the 12 patients experienced relief of the symptoms associated with Paget''s disease. The initial therapy of synthetic human calcitonin 0.5-1.0 mg subcutaneously was administered daily until the alkaline phosphatase had declined to a plateau response; the dose was then decreased to thrice weekly. The major biochemical findings were a 47 percent fall in serum alkaline phosphatase and a comparable decline in 24-hour urinary hydroxyproline. Two subjects discontinued therapy because of side effects; persistent nausea and vomiting in one and a cutaneous allergic reaction in the other. Other side effects were minor. Preliminary results suggest that some patients will maintain the same biochemical response on the reduced dose but that this is not predictable by pre-treatment data. We conclude that synthetic human calcitonin is a safe and effective treatment for Paget''s disease of bone. Preliminary results suggest that the dose and frequency of administration of this agent must be individualized.     

Epidural Administration of Morphine Postoperatively for Morbidly Obese Patients

Two groups of morbidly obese patients undergoing a gastric stapling procedure were compared. Patients in group I received 5 mg of morphine through a lumbar epidural catheter immediately after the surgical procedure while group II patients were treated conventionally with parenterally administered morphine. In group I less narcotics were needed and patients were able to walk earlier than in group II. Length of hospital stay, time to removal of the nasogastric tube and postoperative pulmonary function were not significantly different between groups. Two patients in group I and one patient in group II had generalized pruritus, and in one study patient bradypnea developed in association with the epidural administration of morphine. It is concluded that morbidly obese patients can benefit from epidurally administered morphine and that this form of therapy has a role in the management of these patients.     

The gonadotropin releasing hormone stimulation and the clomiphene tests in female patients with anorexia nervosa.

In 9 female patients suffering from acute anorexia nervosa (a.n.) and in two patients in whom this disease had reached the remission phase, the response of the gonadotropin-producing cells in the adenohypophysis was checked by administration of Gn-RH and the degree to which the hypothalamic-hypophyseal axis could be stimulated was checked by administration of clomiphene (5 x 100 mg). Hormonal screening examinations (cervical score after Insler and hormonal vaginal cytology) were used to assay the basal estrogen production. LH and FSH concentrations in the serum were determined radioimmunologically using the principles of the double antibody technique. The gonadotropin-producing cells did not respond to Gn-RH administration in 8 of the 9 patients with acute a.n. The response was disturbed in one of these patients. The response to Gn-RH stimulation was normal in the two patients in the remission phase. Clomiphene had no stimulatory effect on the hypothalamic-hypophyseal axis during either the acute or remission phase. Hormonal treatment during the acute phase of a.n. is not indicated since, after recovery of a normal body weight, the symptoms recede and the cycle normalises spontaneously.     

Enhanced sensitivity to methadone in adult rats perinatally exposed to methadone

Adult rats, maternally exposed to methadone during gestation and/or lactation, were evaluated for thermoregulatory and nociceptive responsiveness following a challenge with 5 mg/kg (i.p.) methadone. Prior to drug administration, female rats in the gestation and gestation-lactation groups and all male rats perinatally exposed to methadone were subnormal in body temperature. One hour after acute methadone injection, male control rats were hypothermic. All groups of methadone-treated offspring exhibited a marked lowering in body temperature with respect to their pre-injection levels, as well as in regard to values of methadone-administered control animals. Prior to drug administration, male rats of the gestation-lactation group and female rats of the gestation and lactation groups had elevated nociceptive thresholds. Except for male rats in the lactation group, animals treated with methadone perinatally had longer latencies in response to the hot-plate relative to their pre-injection values, as well as to levels of methadone-injected controls. Three days after acute methadone administration, some groups of rats subjected to this drug during gestation and/or lactation were found to be hypothermic and hypalgesic in respect to their pre-injection values, and also relative to control rats. These results suggest that exposure to methadone early in life can have a profound influence on drug response in adulthood.     

Pharmacological administration of granulocyte/macrophage-colony-stimulating factor is of significant importance for the induction of a strong humoral and cellular response in patients immunized with recombinant carcinoembryonic antigen

Eighteen colorectal carcinoma patients without macroscopic disease after surgery were immunized using recombinant (r) human (h) carcinoembryonic antigen (CEA) with (n = 9) or without (n = 9) the addition of soluble granulocyte/macrophage-colony-stimulating factor (GM-CSF). The dose of rhCEA per immunization was 100 μg (n = 6), 316 μg (n = 6) or 1000 μg (n = 6). rhCEA was given s.c. on day 1 and 80 μg/day of GM-CSF s.c. on days 1–4. The schedule was repeated six times during a period of 9 months. All patients in the GM-CSF group developed a strong rhCEA-dose-dependent IgG antibody response while only one-third of the non-GM-CSF patients mounted a weak antibody response. All patients (9/9) in the GM-CSF group developed a strong rhCEA-specific proliferative T cell response as well as type I T cells (interferon γ secretion). In 45% of the patients also a weak type II T cell response (interleukin-4 secretion) was evoked. Both MHC-class-I- and -II restricted rhCEA-specific T cells were noted. A specific cellular response (proliferation and/or cytokine secretion) against native hCEA could be found in 8/9 patients in the GM-CSF group, although at a significantly lower level than against rhCEA. In the non-GM-CSF group a weak rhCEA-specific T cell response was induced. Three patients had a proliferative response, 4 patients type I T cells and 6 patients type II T cells. No signs of autoimmune reactions were noted. Local pharmacological administration of GM-CSF seemed to be a prerequisite for the induction of a strong immunity against baculovirus-produced hCEA protein. However, the cellular response against native CEA was of a significantly lower magnitude. Received: 13 November 1997 / Accepted: 21 May 1998     

Plasma somatomedin activity and urinary hydroxyproline excretion during administration of human growth hormone in children with short stature. Short-term effects

15 prepubertal children with short stature and varying peak growth hormone (GH) levels were given daily injections of increasing doses of human growth hormone (hGH) for consecutive periods of 7 days. Somatomedin activity (SM-act) and total urinary hydroxyproline excretion (THP) were determined in each period. In patients with a varying degree of GH deficiency, but without non-pituitary dependent abnormalities, there was a high correlation between basal SM-act and height velocity. Patients with catch-up growth had an unproportionally low SM-act and the Prader-Willi and transient Cushing patients had an unproportionally high one. All patients showed increases of SM-act and THP on hGH administration, but there was considerable variation of the shape of the curve and of the amplitude of the response. 3 1/2 days after the last injection, SM-act was back to basal level. There was a good correlation between weight-for-height and SM-act during the first two hGH doses, which fits the hypothesis of GH and insulin synergism on SM generation.     

Oxidative Status in Chronic Hepatitis C: The Influence of Antiviral Therapy and Prognostic Value of Serum Hydroperoxide Assay

The effect of α-interferon (α-IFN) and ribavirin (RBV) treatment on oxidative status in chronic hepatitis C (CHC) is unknown.

Aim: To study the time course of oxidative status in patients with CHC during α-IFN and RBV administration, and to evaluate the role of oxidative status in order to predict the therapeutic response.

Patients and methods: Fifty one patients with CHC were studied. All received a combination of α-IFN and RBV for 6 or 12 months in relation to the type of response. The hydroperoxides concentration in serum test samples by D-ROM test was measured in all of the patients before therapy. In 27 patients, hydroperoxides were also measured during the treatment and during the 12 subsequent months.

Results: Cross-sectional analysis demonstrates that patients with a successive long-term response had a lower basal serum hydroperoxide concentration than non-responders (280±40.8 vs 337±83 CARR Units, p<0.05). This resulted to be an independent factor predictive of long-term response in the multi-varied analysis. Longitudinal observation on 27 patients showed that the mean hydroperoxide concentration decreased significantly during treatment (T⁰ 329±79.2 vs T¹² 272±34.5 CARR Units) and that the decrease in the mean values was mainly due to variations in the relapsers group.

Conclusions: Normal basal hydroperoxide concentration helps to predict long-term response to combination therapy. The D-ROM test may be used for screening patients before treatment.     

Comparison of efficacy of different route of administration of chemotherapy on unresectable, advanced gastric cancer

ABSTRACT: BACKGROUND: The aim of this study was to compare the efficacy of two neoadjuvant chemotherapies (FLEEOX and XELOX) with different routes of administration for unresectable gastric cancer. METHODS: A total of 85 patients with unresectable gastric cancer hospitalized from January 2007 to December 2009 received neoadjuvant chemotherapy. The FLEEOX group (48 patients) received the FLEEOX regimen(fluorouracil, leucovorin, epirubicin, epotoside, and oxaliplatin), which combined arterial with venous administration for one or two cycles, while the XELOX group (37 patients) received XELOX (capecitabine plus oxaliplatin) via venous administration for two to four cycles. The clinical response and overall survival of the two groups were compared. RESULTS: In the FLEEOX group, the clinical response rate (RR) of chemotherapy was 85.4% (41 of 48 patients) and the median survival time was 25 months. The 1-year and 2-year disease-free survival (DFS) rates were 85.4% and 45.8%, respectively. In the XELOX group, the clinical RR was 59.5% and the median survival time was 9 months, while the 1-year and 2-year survival rates were 35.2% and 8.3%, respectively. The clinical RR, the R0 resection rate, the median survival time, and the 1-year and 2-year DFS rates were significantly better (P <0.05) in the FLEEOX group than in the XELOX group. In addition, there were no significant differences in the rates of toxic and adverse reactions or post-operative complications between the two groups. CONCLUSIONS: For patients with a preoperative diagnosis of unresectable gastric cancer, the efficacy of the FLEEOX regimen, which combines arterial with venous administration, was better than that of the XELOX regimen, using venous administration only. This combination of arterial and venous administration could be useful for improving the efficacy of neoadjuvant chemotherapy for gastric cancer.     

Treatment of neuroblastoma with [131I]metaiodobenzylguanidine: long-term results in 25 patients.

From 1984 to 1990 we have treated altogether 25 children with [131I]metaiodobenzylguanidine (131I-MIBG) for a refractory, relapsed or metastasized neuroblastoma. Three children had stage III and 22 children had stage IV of the disease; at diagnosis their ages were between 4 months and 10 years. Children with stage III disease had at diagnosis a median age of 3.0 years and at treatment 3.8 years. After first-line chemotherapy 2 children had achieved a complete remission (CR), while in 1 child the tumor did not respond (NR) to the initial treatment. At the time of 131I-MIBG treatment 2 children had relapsed and in the other one no further response was achievable. The children were treated by a 13.5 +/- 12.9 mCi/kg BW per course with a mean total dose of 280.7 +/- 243.9 mCi. One child achieved CR by 131I-MIBG alone, while in 2 cases no measurable success was observed. All 3 children were treated additionally by surgery, chemotherapy and bone marrow transplantation (BMT). Two children have died but one is alive and in CR. The 22 children with stage IV disease were treated in two different study groups. In group A, 14 children were studied for side-effects and response to 131I-MIBG. All children were pretreated with standard chemotherapy. Five were treated in relapse, 5 in progression and 3 at a refractory state of the disease; only 1 child was in complete remission when being treated with 131I-MIBG. Group A patients were treated with a mean of 2.4 courses, with 10.3 mCi/kg BW for each course.(ABSTRACT TRUNCATED AT 250 WORDS)