THE EFFICACY OF INTRAVESICAL BACILLUS CALMETTE-GUERIN IN THE TREATMENT OF INTERSTITIAL CYSTITIS: LONG-TERM FOLLOWUP

Purpose

Interstitial cystitis is a severe debilitating bladder disease characterized by unrelenting pelvic pain and urinary frequency. A prospective, double-blind, placebo controlled study of the use of intravesical bacillus Calmette-Guerin (BCG) in the treatment of interstitial cystitis was recently completed with a mean followup of 8 months. Results demonstrated a 60% BCG response rate, compared to a 27% placebo response rate. We now report the long-term followup results of those patients who received intravesical BCG.

Materials and Methods

Subjects randomized to receive BCG were followed at routine intervals with questionnaires and voiding diaries identical to those in the blinded study. Adverse events were closely monitored in the treatment and followup phases of the study. Subject baseline values were compared to followup data.

Results

Of the BCG responders mean followup was 27 months (range 24 to 33), and 8 of 9 (89%) continue to have an excellent response in all parameters measured. The global interstitial cystitis survey improved 70%, daily voids decreased 31%, nocturia improved 54%, mean voided volume increased 61%, pelvic pain decreased 81%, vaginal pain decreased 71%, urgency decreased 71% and dysuria decreased 82%. Overall well-being improved 54% and the Rand-36 quality of life survey overall improved 64%. In 86% of the patients (6 of 7) dyspareunia resolved. Of the initial BCG nonresponders there was no significant difference in interstitial cystitis symptomatology from baseline to last followup, suggesting that BCG does not worsen interstitial cystitis symptoms. No long-term adverse events from BCG were noted.

Conclusions

Intravesical Tice^* BCG is safe, effective and durable in the treatment of interstitial cystitis. Of those patients who received only 6 weekly treatments and responded favorably 89% continue to have an excellent response with followup ranging from 24 to 33 months.     

INFLUENCE OF REGULAR ALCOHOL CONSUMPTION ON URICAEMIA IN UNSELECTED HEALTHY INDIVIDUALS

We analysed serum uric acid concentrations in a group of healthymale and female volunteers in Córdoba (Spain) possessingvarying nutritional habits, in order to correlate them withtheir usual alcohol intake as measured according to a protocolized,blind dietary questionnaire. There was no significant correlationbetween the serum uric acid and the amount of alcohol regularlydrunk by either male or female individuals. These results suggestthat a moderate alcohol intake has no effect on uricaemia inhealthy individuals.     

Antigen-presenting function of human peritoneum mesothelial cells

Mesothelial cells (MC) from human peritoneal omentum fragments obtained during surgical insertion of peritoneal catheters for continuous peritoneal dialysis in end stage renal failure (ESRF) patients were cultured in vitro. MC exhibited a phenotype different from macrophages, but MHC class II molecules were well expressed. Therefore MC lines were tested for antigen-presenting capacity by pulsing with soluble antigens (tetanus toxoid and purified protein derivative (PPD)) or with a corpusculate antigen (Candida albicans bodies). Autologous peripheral blood mononuclear cells (PBMC) depleted of adherent monocytes and cloned T cells generated from an individual matched for the MHC class II antigen DR2 were used to test antigen-presenting function. MC effectively presented the soluble and corpusculate antigens to autologous and MHC-compatible allogeneic lymphocytes, indicating that they are endowed with both endocytic/phagocytic activity and with processing/presenting capacity. Preincubation of MC with human recombinant interferon-gamma (IFN-γ) up-regulated MHC class II and intercellular adhesion molecule-I (ICAM-I) expression, but the effect on antigen-presenting function was not consistent. Since MC are an important component of the peritoneal environment, they may participate, along with macrophages, in activation of specific T cells and in the generation of local cell-mediated immunity to various pathogens.     

INVERSE EXPRESSION OF mdr 1 AND c-myc GENES IN A RHABDOMYOSARCOMA CELL LINE RESISTANT TO ACTINOMYCIN D

Cytotoxic agents used in cancer therapy may induce differentiation in tumour cells with no proliferative potential. However, chemotherapy can also induce multidrug resistance, a formidable obstacle to the successful treatment of tumours. Both events were recently shown to occur in a rhabdomyosarcoma cell line (RD-DAC) resistant to actinomycin D, a drug of choice in the treatment of these tumours. To analyse this connection, cell line RD cultures were investigated with progressive concentrations of actinomycin D and it was shown that a minimum dose (1·2×10⁻⁶ mm) of the drug was necessary to increase mdr 1 mRNA in RD-DAC. The mechanism of mdr 1 overexpression was an increase in the number of copies of the mdr 1 gene, although the mRNA levels were not correlated with mdr 1 amplification. Drug resistance mediated by mdr 1 overexpression coincided with the development of myogenic differentiation in RD-DAC and with a decrease in c- myc mRNA levels, whereas levels of N- myc mRNA showed no modulation. These findings suggest that factors implicated in cell proliferation and differentiation, such as c- myc , may be responsible for the control of genes related to the development of multidrug resistance in rhabdomyosarcomas. Modulation of these factors may determine the sensitivity of rhabdomyosarcoma cells to drugs and may play an important role in triggering the differentiation programme found in these resistant rhabdomyosarcoma cells.     

Peptides from chiral Cα,α-disubstituted glycines

The molecular and crystal structures of one derivative and three model peptides (to the pentapeptide level) of the chiral C^α,α-disubstituted glycine Cα-methyl, Cα-isopropylglycine [(αMe)Val] have been determined by X-ray diffraction. The derivative is mClAc-l -(α Me)Val-OH, and the peptides are Z-l -(αMe)Val-(l -Ala)₂-OMe monohydrate, Z-Aib-L-(αMe)Val-(Aib)₂-OtBu, and Ac-(Aib)₂-l -(αMe)Val-(Aib)₂OtBu acetonitrile solvate. The tripeptide adopts a type-I β-turn conformation stabilized by a 1 ← 4N-H . O=C intramolecular H-bond. The tetra- and pentapeptides are folded in regular right-handed 3₁₀-helices. All four L-(αMe)Val residues prefer φ, Ψ angles in the right-handed helical region of the conformational map. The results indicate that: (i) the (αMe)Val residue is a strong type-I/III β-turn and helix former, and (ii) the relationship between (αMe)Val chirality and helix screw sense is the same as that of Cα-monosubstituted protein amino-acids. The implications for the use of the (αMe)Val residue in designing conformationally constrained analogues of bioactive peptides are briefly discussed.     

Who pays for measles? The economic arguments for sustained immunization

Increasing international commitment to Universal Child Immunization(UCI) intensifies pressures on already scarce health resources.The costs of the 1989/90 measles epidemic were measured in theState of Guerrero, Mexico, from the perspective of the healthservices and 43 representative communities. Financial loss wasincurred from illness in families of 70% of the 1211 measlescases in a study population of 50294. Some 30% of these familiesdid not have sufficient cash reserves and sold labour, farmanimals or other assets. Among those families, 20% took loansin order to pay the health care costs of their children's measles,19% sold grain stores and 4% indentured their future labour. Standardizing household expenditure on local labour costs, itwas possible to quantify out-of-pocket expenditure and lossof work time. The average cost of a measles case to the communityamounted to the local equivalent of 18.8 work days of an unskilledlabourer, with 27 work days per household affected, excludingincome foregone due to early deaths. Hastings and colleaguescalculated the average cost of measles to British families in1985 to be UK£11.09, considerably less than a day's wagefor a British unskilled labourer at that time. Applying thecosts in the 43 communities to the whole State of Guerrero,without placing a cash value on some 4000 children aged underfive who died from measles, the epidemic cost the communitythe equivalent of 1.6 million work days. The health servicesspent 10% of this value on the epidemic. The cost of vaccinatingall children in the State could be sustained for five years,and increase by 10% per year, and it would still be lower thanthe economic cost of an epidemic to the communities.     

Echocardiographic Aspects of Restrictive Cardiomyopathy

Background and Methods: We studied 17 patients with restrictive cardiomyopathy; eight had biventricular restriction (type A), four had left ventricular restriction (type B), and five had only right ventricular restriction (type C). Results: Type A disease was characterized by pulmonary and systemic venous congestion. The restrictive pattern was found in the inlet of both ventricles. Both atria were enormous, with small or normal-size ventricles. Differential diagnosis included constrictive pericarditis and systolic pump dysfunction. Type B restriction disease was characterized by venous pulmonary congestion, pulmonary hypertension, and important dilatation of the left atrium and right cavities with a small or normal-size left ventricle; the restrictive pattern was found only in the affected left ventricle. Conclusions: The clinical picture resembles that of rheumatic mitral valve disease with right ventricular failure. Type C disease had restriction only in the inlet of right ventricle, with giant right atrium, systemic venous hypertension with low flow, and normal pressure of pulmonary artery and left heart. Differential diagnosis included Ebstein's anomaly of tricuspid valve. The etiology of type A disease was amyloid, endomyocardial fibrosis of ventricles and idiopathic interstitial fibrosis. Asymmetric types were always caused by Davies' disease.     

Entrainment of Ventricular Tachycardia by Sinus Rhythm

Entrainment of ventricular tachycardia (VT) may be manifest as fixed and progressive QRS fusion with ventricular and, rarely, atrial pacing. Only a single example of spontaneous VT entrainment by another rhythm, rapid atrioventricular nodal tachycardia, has been reported. This article describes an example of fixed and progressive QRS fusion between conducted sinus rhythm and VT consistent with entrainment. In contrast to entrainment with pacing, entrainment of VT by sinus rhythm occurred with drug-mediated arrhythmia slowing and demonstrated progressive QRS fusion at a constant cycle length. However, it did not demonstrate unfused but entrained QRS complexes. The resulting short PR interval and wide QRS mimicked a preexcited rhythm.