Breakdown of mucosal defences in congestive gastropathy in cirrhotics

The gastric mucus-bicarbonate barrier, the first line of mucosal defence, has been evaluated in patients with congestive gastropathy and cirrhosis of the liver. Fourteen cirrhotic patients of both sexes (Child's class A or B), with or without oesophageal varices, but with endoscopic signs of congestive gastropathy, and a matched group of healthy controls were studied. The amount of luminal mucoproteins, a Mucoprotective Index as a qualitative assessment of mucus secretion and the output of gastric bicarbonate were determined in basal conditions. In patients with congestive gastropathy a significant (p < 0.01) reduction in all the above parameters was observed, suggesting a substantial impairment of the gastric mucus-bicarbonate barrier. Whether this is an independent phenomenon or a consequence of altered local microcirculation remains to be determined.     

Treatment of hemorrhagic lupus pneumonitis with plasmapheresis

Pulmonary hemorrhage is a rare and often fatal complication of systemic lupus erythematosus (SLE). Treatment with high-dose steroids and cyclophosphamide has been of only modest value, with a reported mortality of up to 92%. We have recently seen three patients with active SLE who developed acute life-threatening pulmonary hemorrhage. Diagnostic evaluation of these patients showed negative sputum and blood cultures, negative glomerular basement membrane antibodies, and negative antineutrophilic cytoplasmic antibodies. In two patients, an open-lung biopsy was performed, and histological examination showed granular alveolar immunofluorescence staining for immunoglobulin and complement components. Treatment with plasmapheresis was initiated with prompt resolution of symptoms and clearing of chest radiograph. Two patients had recurrent bleeds despite treatment with cyclophosphamide and high-dose steroids and required repeated intubation. Plasmapheresis resulted in rapid radiographic and clinical improvement on each occasion. Two patients survived long-term and are presently without pulmonary problems; one patient died of sepsis after initial response to plasmapheresis. The dramatic improvement of the pulmonary disease in these patients leads us to conclude that rapid initiation of plasmapheresis should be strongly considered in SLE patients with severe, life-threatening pulmonary hemorrhage.     

Treatment of congestive heart failure with beta-methyldigoxin (lanitop)

Methylated Digoxin preparation--beta-Methyldigoxin (Lanitop) was used in 50 patients with congestive heart failure of different etiology (tablets of 0.3--0.6 mG per day). Its employment proved very effective in the treatment of congestive heart failure. It is not contraindicated to patients with chronic coronary insufficiency with underlying athrosclerotic cardiosclerosis with signs of congestive circulatory insufficiency. Side-effects of beta-Methyldigoxin are mild and noted rather seldom.     

Familial study of patients with hereditary hemorrhagic telangiectasia

Rendu-Osler-Weber's disease or Hereditary Hemorrhagic Telangiectasia (HTT) is an autosomal dominant hereditary clinical entity characterized by the presence of telangiectasias on skin, mucous membranes and internal organs. The incidence of hepatic, pulmonary or cerebral complications justifies an early diagnostic. A familiar study of patients previously diagnosed of HTT in our hospital was made, establishing a protocol for the identification of asymptomatic or pauci-symptomatic cases. Fourteen patients were studied: 6 with a previous diagnostic, and 8 familiar contacts. Penetrance was of 85%. Epistaxis (80%) and telangiectasias on skin were the most frequent clinical findings. The visceral lesions found were gastrointestinal (28%), hepatic (15%), urological (15%) and pulmonary (7%). All patients were included in an hepatitis B virus vaccination program. It was also made a morphological study with Werhoeff's staining of the elastic layer, that allowed to distinguish both arterial and venous alterations.     

Treatment of recurrent inguinal hernia by implantation of a pre-peritoneal prosthesis. Results of a prospective study

44 patients with 47 recurrent inguinal hernias entered a prospective study. All patients were operatively managed by a standardized technique using a polypropylene (Prolene) mesh inserted through a pre-peritoneal approach. Operating in the pre-peritoneal space avoids dissection of the scared cord and the "inlay" prosthetic mesh safely creates a new "fascia transversalis" with a low rate of recurrences. All patients were personally controlled every 6 months with a follow-up time of 12 to 60 months (mean 20.2 months). The low postoperative morbidity included only one seroma, no infection and no testicular complications. We observed one recurrence occurring 6 months after surgery (2%). The described operative technique using an inlay patch is recommended as the therapy of choice in all recurrent groin hernias.     

Pilot study of a treatment for psychological depression.

Assessed and treated depression (defined as a dysphoric subjective condition reaction to a loss of reinforcement) using a functional problem-solving approach. 22 undergraduates seeking counseling completed the MMPI D scale and the Self-Rating Depression Scale in Exp I, and 28 in Exp II. Exp II replicated Exp I except that an expectancy manipulation about the effectiveness of treatment was added. Treatment was the only variable associated with significant improvement. Suggestions for further research using different population and treatment components are presented. (23 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Pilot study on the effectiveness of systematic desensitization with neurologically impaired children with phobic disorders.

A modified version of J. Wolpe's systematic desensitization therapy involving direct confrontation with the fear-inducing stimulus was attempted with 30 neurologically impaired children with phobic symptoms. 2 hypotheses were tested: (a) a nonverbal therapeutic technique not requiring motivation will produce successful symptom reduction for these Ss, and (b) awareness of therapeutic procedure is not necessary for successful results. Both hypotheses were confirmed. (23 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A case of protein-losing gastropathy associated with autoimmune mechanism

Injection of kappa-agonist dynorphins and non-peptide kappa-agonists into the hippocampus induces a reduction in blood pressure. It has been postulated that kappa-opioid agonists and kappa-receptors are important in one mechanism of antihypertension and might have clinical potential for the treatment of hypertension. We have investigated whether chronic treatment with U-50488H and U-62066E, two non-peptide kappa-agonists, effects brain kappa 1- or kappa 2-receptor numbers or affinities in areas that might correlate with changes in blood pressure. kappa 1- and kappa 2-Opioid receptor affinities and densities were determined in cortex, hippocampus, hypothalamus, midbrain and pons after 14 days subcutaneous infusion of two non-peptide kappa-agonists, U-50488H and U-62066E, 9.6 mg kg day-1, by means of osmotic minipumps, to spontaneously hypertensive rats (SHR) and to Wistar-Kyoto (WKY) rats. This infusion significantly reduced blood pressure. Brains were removed within 48 h of the end of drug infusion and kappa-receptor binding studies were performed on homogenates from each brain area using [3H]U-69593 to assay kappa 1-receptors and [3H]bremazocine to assay kappa 2-receptors. U-62066E treatment seemed to cause a slight decrease in the number of [3H]bremazocine binding sites (kappa 2-receptors) from 98.2 +/- 9 to 74.9 +/- 8 fmol (mg protein)-1 in the hippocampus when compared with SHR controls. A small decrease in kappa 2-receptor density in the pons of WKY rats was also observed after U-50488H treatment (control, 51.2 +/- 5; U-50488H-treated, 24.3 +/- 9 fmol (mg protein)-1. Although SHR blood pressure values were consistently reduced by treatment with kappa-agonists, there was little if any significant change in apparent numbers of kappa 1- or kappa 2-receptors or their affinities in any of the brain regions examined. These data indicate that although chronic treatment with kappa-agonists reduces blood pressure in SHR, the treatment does not elicit major changes in brain kappa-receptors either in SHR or in WKY rats. The potential use of kappa-agonists for treating hypertension might not cause receptor changes in the brain and might, therefore, result in fewer side effects or negligible rebound hypertension.     

Domperidone. A review of its use in diabetic gastropathy

Domperidone is a selective antagonist at peripheral dopamine D2 receptors, with gastroprokinetic and antiemetic properties. It increases the frequency and duration of antral and duodenal contractions, thus decreasing/improving transit time of food through the gastrointestinal tract. Gastric emptying of liquids and solids is significantly improved with oral domperidone 40 to 120 mg/day in patients with diabetic gastropathy. Oral domperidone 40 to 80 mg/day significantly decreased the severity of symptoms of gastropathy from baseline values in 66 to 88% of patients with type 1 (insulin-dependent) or insulin-requiring diabetes mellitus. Double-blind withdrawal of domperidone from patients who had responded previously led to greater deterioration of symptoms in patients with delayed gastric emptying than in those who continued receiving the drug. Quality of life was significantly improved in patients who showed a symptomatic response to domperidone. The administration of domperidone 40 to 120 mg/day significantly reduced hospitalisation rates in patients with gastropathy. The symptomatic improvement with domperidone 80 mg/day was similar to that seen with cisapride 40 mg/day or metoclopramide 40 mg/day, and therapeutic benefits seen in symptoms of gastropathy were maintained with domperidone for up to 12 years. Domperidone 40 to 80 mg/day may be effective in patients who are refractory to metoclopramide, and a combination of domperidone 80 mg/day with cisapride 80 mg/day may improve some symptoms in patients who do not respond to either agent alone. Domperidone 40 to 120 mg/day was well tolerated for periods up to 12 years in trials in patients with diabetic gastropathy. Adverse events with domperidone 80 mg/day were similar to those seen in placebo recipients and significantly fewer than in patients receiving metoclopramide 40 mg/day. Although significant elevation of plasma prolactin levels (unrelated to dosage and duration of treatment) occurred in all domperidone recipients, prolactin-related adverse events were observed in only 10 to 20% of patients. CONCLUSIONS: The available data suggest that domperidone 40 to 80 mg/day is an effective agent for the management of symptoms of gastropathy in patients with type 1 diabetes mellitus. In addition, it may provide symptom improvement in patients with gastropathy refractory to other gastroprokinetic agents. Domperidone maintains efficacy in the long term (up to 12 years) and appears to have a better tolerability profile than metoclopramide 40 mg/day.     

A placebo-controlled study of growth hormone in patients with congestive heart failure

AIM: Experimental data in heart failure models and an open trial of seven patients with idiopathic dilated cardiomyopathy have suggested beneficial effects of growth hormone on cardiac function. The aim of the present study was to evaluate growth hormone effects on cardiac function in a placebo-controlled study. METHODS: Twenty two patients with congestive heart failure of different aetiologies in NYHA II and III and an echocardiographic ejection fraction <0.45 were studied in a 3 month double-blind placebo-controlled study with growth hormone added to optimal heart failure therapy. Patients received either placebo (n=11) or recombinant human growth hormone (n=11) in an initial dose of 0.1 IU x kg(-1) week(-1) for 1 week, and thereafter 0.25 IU x kg(-1) week(-1) for the rest of the treatment period. Cardiac function was assessed by equilibrium radionuclide angiography and Doppler echocardiography. Functional capacity was evaluated by computerized bicycle exercise electrocardiography. RESULTS: Recombinant human growth hormone had no significant effect on systolic or diastolic cardiac function, exercise capacity or neuroendocrine activation. In addition, there was no overall improvement in functional class or dyspnoea grade. Insulin-like growth factor-I significantly increased demonstrating that the growth hormone had an endocrine effect. CONCLUSION: This is the first double-blind and placebo-controlled study of the administration, over 3 months, of recombinant human growth hormone in patients with congestive heart failure of different aetiologies. The treatment was safe and without serious side effects. However, no beneficial effects on cardiac function or structure could be detected.     

Treatment of articular cartilage defects of the knee with autologous chondrocyte implantation

alpha 1-Adrenergic receptor-mediated responses are overwhelming in adult rat hepatocytes. Inversely, beta-responses are predominant over alpha 1-responses in the hepatocytes that have been cultured at a low cell density (10(4) cells/cm2) for 24 h. The insulin-EGF-induced DNA synthesis in the beta-response-dominant hepatocytes was doubled by beta-agonists or cAMP-generating agents added far behind (16-20 h) the addition of insulin/EGF; i.e., immediately before the entry into the S-phase of the cell cycle. Agonists of alpha 1-adrenergic or other Ca2+, mobilising receptors added to the alpha 1-response-dominant hepatocytes increased DNA synthesis only if they were added within 1-2 h after the addition of insulin/EGF, at the early stage of G1-phase. Agonists of "non-dominant" receptors were rather antagonistic to agonists of "dominant" receptors. Thus, agonists of alpha 1-adrenergic (and other Ca2+ mobilising) receptors and agonists of beta-adrenergic (and other cAMP-generating) receptors acted as comitogens in their own particular manners in the presence of growth factors in hepatocytes in which the respective receptor functions were dominant.     

Peritumoral administered IL-2-induced tumor regression in melanoma. Pilot study

Since the immune system plays an important role in the rejection of tumours, current tumour therapy includes immunostimulation. This can be done by interleukin 2 (IL-2), which activates T and killer cells and induces lysis of the tumour. Because the intravenous application of IL-2 may have serious side effects, we treated two patients with peritumoral injections in a pilot study. Both patients suffered from multiple cutaneous metastases of melanoma. A total of 31 and 39 x 10(6) IU recombinant IL-2 (Proleukin) respectively was injected in increasing concentrations in one metastasis of each patient. Histologically, almost complete necrosis of the tumour was induced. In comparison with the control specimen, the T-cell-rich infiltrate increased intra- and, in particular, peritumorally. While the ratio of helper to suppressor T cells remained unchanged, the proportions of NK cells, monocytes/macrophages and IL-2-receptor-bearing cells increased. This reaction was restricted to treated metastases. No clinical side effects or laboratory changes were registered apart from local erythema and swelling.     

Follow-up of TIPS: evaluation of signs of dysfunction with Doppler ultrasonography

The anemia of malignancy is common and is related to several etiologic factors, a major one being relative erythropoietin (Epo) deficiency. Blood transfusions, the traditional therapy, provides a quick solution but is associated with complications. This was the rationale for recombinant human Epo (rHuEpo) in the treatment of anemia of cancer. Over the past few years, about 20 publications have reported the results of rHuEpo in the treatment of cancer-associated anemia in more than 850 patients with a variety of malignancies. In general, more than half of the patients responded with a significant increase in their hemoglobin level, a decrease in blood transfusion requirements, and an improved performance status and quality of life. About 4 weeks are required till the onset of effect. The hormone is well tolerated with minimal adverse effects and subcutaneous injections appear to be the preferred method of administration. Additional studies will hopefully answer several questions including optimal dosage and duration of treatment, Epo resistance, and the possibility of predicting the response.     

Pilot study of pathophysiology of constipation among community diabetics

We aimed to compare gastrointestinal transit and defecatory function in a random sample of people with or without diabetes mellitus in a US community who reported constipation or laxative use. In this pilot study we measured: gastric, small bowel, and colonic transit by scintigraphy; vector manometry of anal sphincters at rest and during squeeze; defecatory dynamics by balloon expulsion test; and scintigraphic measurement of anorectal angle at rest and during defecation. Autonomic function tests were performed in diabetics. Diabetics with constipation had a higher prevalence of abnormal evacuation or prolonged colonic transit during the first 24 hr than controls (P = 0.07): three had prolonged 24-hr colonic transit, and three abnormal evacuation. Among constipated controls, only one had anismus. Overall, diabetics had slower colonic transit during the first 24 hr than nondiabetics (P < 0.05). Community diabetics who experience constipation or use laxatives have a greater prevalence of delayed 24-hr colonic transit or evacuatory dysfunction than community controls.     

Pilot study of anti-lipopolysaccharide human monoclonal antibody MAB-T88 in patients with gram-negative sepsis

8 cases of malignant choroidal melanoma were treated with argon and krypton laser photocoagulation of average 11 sessions and followed up an average 56 months. Clinical complete regression was observed in 5 cases (62.5%), in whom the tumors measured from 1.0mm x 1.2mm x 1.5mm to 6.0mm x 4.5mm x 2.5mm. The other 3 cases (37.5%) recurred, in whom the tumors measured from 4.0mm x 2.0mm x 3.5mm to 11.5mm x 12.5mm x 3.5mm. The complications of treatment included branch retinal vein occlusion, retinal neovascularization, vitreous hemorrhage, macular edema and optic atrophy. These results suggested that laser photocoagulation was useful in the treatment of small malignant choroidal melanomas.