Pattern of postprandial carbohydrate metabolism and effects of portal and peripheral insulin delivery

The importance of portal insulin delivery in the regulation of postprandial carbohydrate metabolism is uncertain. To address this question, three groups of dogs were studied: one group in which pancreatic venous drainage was transected and reanastomosed (portal insulin delivery), one in which the pancreatic drainage was transected and anastomosed to the inferior vena cava (peripheral insulin delivery), and one that received only a sham operation. Plasma insulin was greater (P less than 0.05) during peripheral insulin delivery than in either the portal or sham groups, respectively, before and after meal ingestion. On the other hand, C-peptide concentrations did not differ between groups, resulting in a higher (P less than 0.001) insulin to C-peptide ratio in the peripheral group. This indicated that the hyperinsulinemia in the peripheral group was due to decreased insulin clearance rather than increased insulin secretion. Isotopically determined splanchnic uptake of ingested glucose, postprandial suppression of hepatic glucose release, incorporation of CO2 into glucose (a qualitative measure of gluconeogenesis), and total-body glucose uptake were virtually identical in all groups. Similarly, plasma lipid, beta-hydroxybutyrate, and lactate concentrations did not differ between groups. Our data indicate that, despite differences in systemic insulin concentration, portal and peripheral insulin delivery comparably regulate hepatic and extrahepatic carbohydrate metabolism after meal ingestion.     

In VivoStudies of Adenovirus-Based p53 Gene Therapy for Ovarian Cancer

Objectives.To test the safety, efficacy, and toxicity of gene therapy using wild-type p53-expressing adenovirus (Ad-CMV-p53) in a nude mouse model with intraperitoneal (ip) 2774 human ovarian cancer cell line that contains a p53 mutation.Study design.An initial study of adenovirus tolerance was determined in nude mice by a single ip injection of increasing doses of Ad-CMV-p53. Nude mice were implanted with an LD₁₀₀dose of 1 × 10⁷cells. To study the efficacy and specificity of Ad-CMV-p53 treatment, the mice received treatment with different adenovirus constructs. One group received Ad-CMV-p53 and another group received a control adenovirus construct, Ad-CMV-βgal. To study the treatment response to Ad-CMV-p53, the mice were divided into groups and received various treatment schedules of 1 × 10⁸pfu of Ad-CMV-p53.Results.The mice tolerated Ad-CMV-p53 without adverse effects at doses of 1 × 10⁸pfu. The response to Ad-CMV-p53 showed significant survival duration in each dose regimen, with a survival time greater than that of untreated animals (P= 0.0173). However, no statistically significant survival advantage was observed between Ad-CMV-p53- and Ad-CMV-βgal-treated mice.Conclusions.These studies show that at the adenovirus dose and administration regimen used, there is effective but not specific 2774 tumor growth inhibitionin vivo.Efficient introduction of biologically active genes into tumor cells would greatly facilitate cancer therapy. Thus, although promising, these results caution that much effort will be required to realize the potential for clinical application of adenovirus-based ovarian cancer gene therapy.     

Gonadotrophin-releasing hormone agonist therapy for hirsutism is as effective as high dose cyproterone acetate but results in a longer remission

Both cyproterone acetate (CPA) and the gonadotrophin-releasing hormone agonist (GnRHa) have been shown to be effective for the treatment of hirsutism. We wished to compare the effectiveness of CPA in two standard doses with GnRHa and add-back therapy and to compare the length of remission after these treatments. A total of 60 hirsute hyperandrogenic women was assigned to the following treatment groups: CPA 2 mg with 35 microg of ethinylestradiol for 21 days each month (Diane group), CPA 50 mg, days 5-15, and ethinylestradiol 50 microg, days 5-25, each month (CPA group) or Decapeptyl 3.75 mg i.m. every 28 days with the addition of conjugated oestrogen 0.625 mg, days 1-21, and medroxyprogesterone acetate 10 mg, days 12-21 (GnRHa group). Hirsutism was graded by the Ferriman-Gallwey-Lorenzo (FGL) index and anagen hair shaft diameters and serum luteinizing hormone (LH) and testosterone were assessed before and every 3 months during and after treatment. All women were treated for 1 year with 1 year follow-up. At baseline hirsutism and endocrine patterns were similar in all groups. After one year of treatment, hirsutism decreased in all groups but the changes were greater (P <0.05) in the CPA and GnRHa groups than in the Diane group. Serum LH and testosterone were lowest in the GnRHa group. After withdrawal, hirsutism increased rapidly in the Diane and CPA groups and after 6 months, FGL scores and hair shaft diameters were similar to pretreatment values. In the GnRHa group, hirsutism increased more gradually and after 1 year of withdrawal, FGL scores and hair diameters were significantly (P <0.05) less than pretreatment values. Serum LH and testosterone increased rapidly in all three groups reaching pretreatment values by 6 months. These data suggest equal efficacy of the GnRHa and the high dose CPA regimen for the treatment of hirsutism in hyperandrogenic women. GnRHa with add-back treatment appears to result in a longer remission of hirsutism in comparison with CPA.      

Evidence of an abnormal intramuscular component of fatigue in multiple sclerosis

The goals of this study were to investigate muscle fatigue in patients with multiple sclerosis (MS), and to determine the relationships between muscle fatigue, clinical status, and perceived fatigue. The fatigability of the anterior tibial muscle was quantitated in patients and controls during 9 min of intermittent stimulation (used to eliminate central sources of muscle fatigue). During exercise, the decline in tetanic force, phosphocreatine, and intracellular pH was greater in patients than in controls. The compound muscle action potential amplitude did not decrease during exercise, indicating that there was no failure of neuromuscular transmission during fatigue. Thus, the excessive fatigue in MS developed from sources beyond the muscle membrane. Following exercise, the recovery of tetanic force was delayed in patients (a pattern that suggests abnormal excitation–contraction coupling), whereas the recovery of metabolites was complete in both groups. Muscular fatigue was correlated with clinical disability but not with perceived fatigue. These results suggests that fatigue in MS has both central (perception, upper motor neuron dysfunction) and peripheral (impaired metabolism and excitation–contraction coupling) components.© 1995 John Wiley &Sons, Inc.     

Assessment of sexual abuse and trauma: Clinical measures

Examined are several measures currently used in the assessment of child abuse, sexual abuse, and trauma. These measures include structured clinical interviews, self report measures, screening inventory, symptom checklist, and some measures that include decision making properties. Issues and implications for clinical practice are explored.     

Bladder leiomyosarcoma following cyclophosphamide therapy for lupus nephritis

We report 2 cases of leiomyosarcoma of the bladder that occurred after long-term cyclophosphamide chemotherapy for lupus nephritis and rheumatoid arthritis. One patient had a tumor at the end of an 11-year course of chemotherapy and 1 approximately 7 years after completing a 7-year course of chemotherapy. Patient 1 underwent left partial cystectomy and patient 2 underwent cystectomy with ileal conduit urinary diversion. In patient 1 the tumor was a typical leiomyosarcoma and patient 2 had a myxoid variant. Both patients were free of disease at 4 months and 3 years, respectively. Whereas previous reports of the carcinogenic effects of cyclophosphamide have been questioned, since the induced tumors occurred in patients being treated for other neoplasms (lymphoproliferative and myeloproliferative disorders), the disease in both of our patients followed cyclophosphamide therapy for nonneoplastic disorders.     

The ileal neobladder: experience and results of more than 100 consecutive cases

The ileal neobladder produces a completely detubularized, low pressure, high capacity reservoir constructed from ileum without any valves. From April 1986 through May 1989, 113 patients underwent this procedure at our institution. Of these patients 99 underwent simultaneous radical cystectomy for bladder cancer and 14 underwent bladder augmentation. The mean postoperative followup was 14.4 months, with a range of 1 to 36 months. There was no perioperative mortality. However, 7 patients died more than 2 months postoperatively: 5 of tumor progression, 1 of pneumonia and severe metabolic acidosis, and 1 of septicemia of unknown cause. Reoperation was necessary in only 13 patients; 10 patients required urethrotomy or dilation of urethral strictures. Day and night continence was preserved in 82.1% of all patients. Stress incontinence, which must be corrected by an artificial sphincter, was found in 4 patients (4.2%) and night-time incontinence that required an external device occurred in 5 (5.3%). Eight patients (8.4%) with mild stress incontinence required no further treatment. Pressure waves exceeding 22 cm. water seldom occurred and then only at maximum capacity. Our experience with this relatively simple system without a nipple is an overwhelming success. The need for reoperation is extraordinarily low and the high reservoir capacity results in continence from the beginning in most patients. The concept is sound and offers a genuine alternative to any form of cutaneous urinary diversion with an incidence of complications not higher than after standard supravesical urinary diversion.