Vibrational circular dichroism of tetraphenylporphyrin in peptide complexes? A computational study.

The Raman and absorption spectra of tetraphenylporphyrin (TPP) were calculated and compared to experiment. The computation was based on the harmonic molecular force field and electric tensors obtained ab initio at the BPW91/6-31G* level. Good agreement was found between experimental and calculated frequencies and intensities. In order to estimate whether induced optical activity in chiral complexes interferes with the signal of peptide vibrations, the vibrational circular dichroism (VCD) spectra of TPP were simulated. The magnetic field perturbation theory (MFP) and the gauge-invariant atomic orbitals (GIAO) were used for the simulation. Such spectra were compared to theoretical VCD intensities of a model tripeptide as well to experimental spectra of a complex of the peptide and tetrakis(p-sulfonatophenyl)porphyrin (TSPP). No significant contribution to VCD signal from the TPP residue was found in experimental spectra. Thus, possible peptide conformational changes occurring during the complexation can be monitored directly in the amide I frequency region.

[The importance of CAPD in kidney replacement therapy]. / Bedeutung der CAPD für die Nierenersatztherapie.

Continuous ambulatory peritoneal dialysis (CAPD) a method suitable for self-treatment by patients with chronic renal failure, was introduced for clinical use at the end of the seventies. It was rapidly accepted and used worldwide. Based upon a ten-year-old clinical experience at the renal unit of the Stadtspital Waid, Zürich, and on data of a cohort of 113 unselected patients treated by this method, this report aims at the importance of CAPD for renal replacement therapy. Experiences with developments of materials, techniques and measures preventing complications, collected during an observation period, from 1979 to 1989 were analyzed and data from three arbitrarily fixed consecutive periods compared. The Tenckhoff catheter, primarily used for dialysis, has been replaced by the Oreopoulos-Zellermann catheter because of a reduced complication rate. The number of patients treated with CAPD doubled within these ten years. The survival rate for different methods was similar in the three time periods investigated. In accordance with other centers, peritonitis was found to be the most frequent cause for a drop-out and was equally the most frequent complication whose incidence, however, declined over the observation periods. Compared to other centers, incidence of peritonitis was already low before at the renal unit of SWZ. 41% of the patients died, most of them because of cardiovascular problems. Infections of the catheter tunnels were less frequent, but their rate could not be influenced in the course of the ten-year period. Clinical experiences of the first ten years with CAPD at the renal unit of SWZ yielded positive results: 1. CAPD represents a simple and effective method for dialysis therapy of equal value compared to hemodialysis. 2. Success of the CAPD program depends crucially on amelioration of the CAPD materials and techniques as well as on an optimal education of the patient by the nursing staff and the physician. 3. Obviously, the significant decline of the rate of peritonitis in the Stadtspital Waid was due to the introduction of a simple microbiologic method for self-control (so-called dialysate-digest medium tube-method) and to the prophylaxis for fungal peritonitis with Nystatin per os accompanying every antibiotic therapy. 4. A future challenge is seen in increased attention and better prevention of the second most common complication of CAPD, catheter-tunnel infection.

[Continuous ambulatory peritoneal dialysis in the treatment of end-stage renal insufficiency. Current status in 1991]. / Kontinuální ambulantní peritoneální dialýza pri lécbe terminální renální insuficience. Stav v roce 1991.

CAPD was introduced in the U.S.A in 1978 as a new technique of peritoneal dialysis and as a self-treatment method and new possibility of renal replacement therapy in patients with end-stage renal failure. Up to this time peritoneal dialysis stood in the shade of hemodialysis, so that the new technique brought about a true renaissance of peritoneal dialysis. Owing to its advantages CAPD rapidly expanded worldwide and the number of CAPD patients is still increasing. Patients who could not be taken into consideration for renal replacement treatment because of shortage of facilities, could now be accepted in increasing number; a new era of renal replacement therapy began. The article describes the technique, the advantages, disadvantages and the problems regarding the indications for CAPD as is the status in the year 1991.

Successful prophylaxis for fungal peritonitis in patients on continuous ambulatory peritoneal dialysis: six years' experience.

Fungal peritonitis as a serious complication of continuous ambulatory peritoneal dialysis (CAPD) is often associated with severe morbidity, CAPD "drop-out" and, occasionally, death. Most episodes of fungal peritonitis occur during or after a period of antibiotic treatment of various bacterial infections, usually bacterial peritonitis. From April 1979 to December 1982 (period I), 10 episodes of fungal peritonitis occurred during 415 patient-months, ie, 10.5% of all peritonitis episodes recorded in our CAPD program. After the introduction of oral prophylaxis with 3 x 500,000 IU [corrected] nystatin during every course of antibiotic treatment, only four episodes of fungal peritonitis occurred during 2,102 patient-months, ie, 3.1% of all peritonitis episodes from January 1983 to March 1989 (period II). This difference between the first and second periods is significant (P less than 0.05). Moreover, none of the four patients who contracted fungal peritonitis in the second period received nystatin prophylaxis. Thus, the simple measure of oral prophylaxis using this nonabsorbable antifungal agent in every case of an antibiotic treatment largely eliminates the risk of fungal peritonitis in patients on CAPD.

Design and testing of the Baxter Integrated Disconnect Systems (IDS).

This paper describes the result of a miltidisciplinary approach to the design and evaluation of a new CAPD disconnect system: the Baxter Integrated Disconnect System (IDS). This system consists of a bag full of fresh Dianeal, an empty bag for the drainage of spent dialysate and tubings connecting the 2 in a Y fashion. With this system, the patient makes only one connection. The system is disposable. The major property that makes this unique is that all components are preassembled, and the whole system is steam-sterilized as 1 unit. In general, similar systems use different sterilization methods for the various components of the system. Those components are then assembled, under clean conditions by the manufacturer, without final sterilization of the unit. Assembly of the components is sometimes left to the patient. The concept of IDS, therefore, is unique and warrants lower rates of contamination. This system has been tested on patients for a total observation period of 765 patient months, and has proven to be simple, safe and effective. It yields a 63% probability of peritonitis-free patients at 24 months.

[Surgical experiences with the arteriovenous hemodialysis shunt (1970-1988)]. / Chirurgische Erfahrungen mit arterio-venösen Hämodialyse-Shunts (1970-1988).

Data were collected concerning 307 arteriovenous fistula for hemodialysis created in 186 patients between 1970 and 1988 at the Municipal Hospital Waid of Zurich. The average age of all patients was 52.7 years. The procedure which provides access for 97.2% of all patients is the radiocephalic fistula (Cimino-Brescia), which became dilated within 4 weeks in 82.9%. There was a primary failure rate of 11.2%. The patency rate was 60.2% after 3 years and 36.6% after 5 years. Early complications, especially thrombosis, occurred in 11.2% and were caused usually by technical faults or hypotonia. Late complications were discovered in 42.8% of the patients (22.5% thrombosis, 7% stenosis, 2.1% aneurysm, 2.6% infection, 2.7% steal syndrome and 5.9% skin alterations). During the average period of dialysis (4.6 years), 38% of the patients needed more than one fistula. In that situation too, the same radiocephalic fistula was performed in the contralateral forearm (30%) prior to perform advanced procedures like PTFE-grafts (29%), etc. The patency rate after 3 years was 60.4% for radiocephalic fistula and 69.7% for PTFE transplants. The shuntthrombosis was again the main early (9.9%) and late (24%) postoperative complication. With help of a surgical thrombectomy or more conservative procedures like anticoagulation, local thrombectomy and transluminal angioplasty, 81.2%, respectively 64% of the failed fistula could be restored. Other complications like bleeding, aneurysms and infections occurred especially in arteriovenous grafts (0.5-5.7%).

Stomatococcus mucilaginosus as an agent of CAPD peritonitis.

We report a case of bacterial CAPD peritonitis in a 57 year old immunosuppressed woman with renal insufficiency caused by a rare species of the Micrococcaceae, Stomatococcus mucilaginosus. This uncommon case shows that the presence of gram-positive cocci in pairs, tetrads and clusters forming whitish-gummy colonies should remind us of the possibility of Stomatococcus mucilaginosus.

[Diagnostic value of atrial natriuretic peptide in hypertension and heart insufficiency]. / Diagnostische Wertigkeit von ANP bei Hypertonie und Herzinsuffizienz.

Serum ANP levels were measured by radioreceptor assay in 40 patients with various forms of secondary hypertension and 6 patients with heart failure. In addition, serum ANP was determined in 4 patients with renal artery stenosis before and after dilatation, as well as in 5 anephric patients before and after haemodialysis. Our results showed elevated serum ANP level in most patients with various forms of secondary hypertension and chronic heart failure. A distinction between these two groups and a control group of healthy individuals was not possible due to the wide range and occasional normal levels in the first two groups. ANP levels in patients with renal stenosis decreased after dilatation but there was no correlation with the success of this procedure. A positive correlation between ANP and plasma renin level was detectable in patients with renal artery stenosis, but was also elevated in anephric patients with absent renin production. In summary, our results show that measurements of serum-ANP are of little significance in the diagnosis of hypertension and chronic cardiac failure.

[Chronic pancreatitis as a possible result of analgesic abuse]. / Chronische Pankreatitis als wahrscheinliche Folge eines Analgetikaabusus.

Abuse of analgesics (AA) is a well known cause of chronic interstitial nephritis. Recently a noxious effect of AA on the pancreas has been suggested based upon case observations, and first evidence for association of AA with chronic pancreatitis was presented. In the present prospective clinical study 95 patients with chronic renal insufficiency, in 53 of them associated with AA, were investigated for evidence of chronic pancreatitis (e.g. history of pancreatitis, pancreatic calcifications, diabetes and exocrine function). The patients were divided into two groups: group A consisted of 53 patients with chronic nephropathy associated with AA, and control group B consisted of 42 patients with chronic nephropathy of other etiology. Pancreatic calcifications were observed in 5 cases of group A (10%), but in none of the patients of group B. Exocrine insufficiency was found in 2 of the 5 cases with pancreatic calcifications. Only one of the 5 patients had a history of pancreatitis in association with exocrine and endocrine insufficiency. Thus pancreatic calcifications, which are virtually pathognomonic for chronic pancreatitis, were found exclusively in the group with chronic nephropathy due to analgesic abuse. Chronic pancreatitis in this group of patients is likely to be overlooked because of the lack of clinical and laboratory evidence. The present data support our previous observations that AA may be an etiological factor in chronic calcifying pancreatitis. This first evidence for a drug-induced form of chronic pancreatitis is presented.

Thymopentin as adjuvant therapy to hepatitis B vaccination in formerly non-or hyporesponding hemodialysis patients.

Thirteen patients who were on chronic hemodialysis for renal failure received booster vaccination with 40 micrograms HB-Vax while receiving thymopentin as adjuvant therapy. A 50-mg dose of thymopentin was administered subcutaneously 3 times weekly for 3 weeks and vaccination was given after the first week's treatment. Seven of the 13 patients had never developed any measurable anti-HBs titers in spite of 4-5 previous vaccinations, although 6 out of these 7 had used interferon as adjuvants to their last vaccination. The remaining 6 patients were hyporesponders, but the antibodies had vanished in all before the study was started. Twelve out of the 13 patients developed anti-HBs after revaccination while on thymopentin adjuvant therapy. The antibody production started in most cases within 2 weeks after the booster HB-Vax and showed an increasing trend for up to 6 weeks. Protective titers persisted in the responder cases for the duration of the study (2-3 months). Thus thymopentin may represent a valuable tool to achieve a successful hepatitis B vaccination in hemodialysis patients.

Thymopentin as adjuvant to hepatitis B vaccination. Results from three double-blind studies.

The influence of adjuvant thymopentin therapy on the effect of vaccination with HB-Vax was investigated in three independent double-blind studies in which three different time/dose schedules of the adjuvant therapy were used. The first study was conducted with 30 hemodialyzed patients who had previously been non- or hyporesponders. Forty and 26 nonvaccinated hemodialyzed patients were chosen for the two additional studies. A 50-mg dose of thymopentin or placebo was administered subcutaneously in all studies. In one study, in which only one adjuvant injection was administered simultaneously with each vaccine injection, thymopentin inhibited the antibody response. On the contrary, in the other two studies, in which three injections of adjuvant were administered during the week following the vaccination (in one of these studies three injections were also given before the vaccination), no difference in the effect of vaccination was observed in patients on either placebo or thymopentin. Comparison of the results of the present studies with those of earlier observations emphasizes the importance of time/dose schedules of adjuvant therapy in vaccination.

[Non-A, non-B hepatitis in patients with chronic hemodialysis]. / Non-A-non-B-Hepatitis bei chronisch hämodialysierten Patienten.

A prospective study was conducted of the incidence and course of acute viral hepatitis in 69 chronic hemodialysis patients. During a mean observation period of 15.4 months, 5.6 cases/100 patients/year of non-A, non-B hepatitis and 1.1 cases/100 patients/year of hepatitis B virus infection occurred. 19 out of 38 patients with serologic evidence of immunity against hepatitis B virus infection developed the antibody to hepatitis B surface antigen after active immunization. All cases of non-A, non-B hepatitis had an asymptomatic course, but there was a tendency to chronicity. The overall impact of non-A, non-B hepatitis in patients on chronic hemodialysis is discussed.

Control of epidemic meningococcal meningitis by mass vaccination. I. Further epidemiological evaluation of groups A and C vaccines in northern Nigeria.

Mass vaccination campaigns were mounted by several state governments in the northern Nigerian sector of the African meningitis belt. Bivalent groups A and C polysaccharide vaccines were used. The results of these campaigns in four of the states which are adjacent to each other are presented and assessed. A total of 7535350 persons in the four States, Bauchi, Borno, Gongola and Plateau, were given the vaccine over a period of 4 years (1978-1981). There was a decline in the overall number of cases reported as well as in the number of deaths in the area, where, since 1978, there has not been an epidemic of meningococcal meningitis. Variations were observed among the states which vaccinated over 50% of their populations and had many fewer cases than those which did not. These results show that mass vaccination is an effective means of preventing outbreaks of meningococcal meningitis and may lead to eradication of the disease.

PIP: In mass vaccination campaigns organized by several state governments in northern Nigeria in 1978-81, a total of 7,535,350 people received bivalent groups A and C polysaccharide meningitis vaccines in the states of Bauchi, Borno, Gongola, and Plateau. This figure represents 53% of the population of these 4 states, which are part of the African meningitis belt. Of the total number of reported cases of meningitis from the 4 states in the 1978-81 period, 5565 (80%) occurred in 1978. As more persons were vaccinated over the years, the number of reported cases declined significantly in all states but Gongola, where the percentage vaccinated (19%) was lowest. By 1980 in Bauchi, where 78% of the population had been vaccinated, there were only 12 reported cases of meningitis and no deaths, and there has not been a single reported case of the disease in this state since 1981. These findings confirm the effectiveness of mass vaccination in limiting meningococcal infection. Moreover, mass vaccination has the potential of eradicating the disease, unlike selective vaccination. Epidemiologic research suggests it may be necessary to undertake mass vaccination campaigns only among those 3-15 years of age once every 4-5 years.

Corynebacterium group JK peritonitis in patients on continuous ambulatory peritoneal dialysis.

Corynebacterium group JK is described as the aetiologic agent of a second episode of peritonitis which occurred after a period of antibiotic treatment for likely endogenous peritonitis. Inclusion of vancomycin is suggested for treatment of continuous ambulatory peritoneal dialysis (CAPD) peritonitis in patients colonized by these multiresistant bacteria.

Interferon as an adjuvant for hepatitis B vaccination in non- and low-responder populations.

To determine the effect of interferon on the production of antibodies against hepatitis B virus, recombinant alpha-interferon was added only to the fifth vaccine injection in a non-responder group and to all three initial vaccine injections in a low-responder group. In the non-responder group, 27% of the hemodialysis patients, 7% of the renal transplant patients, and both medical staff members tested developed low serum concentrations of anti-HBs (less than 25 mU/ml). Whereas in the low-responder group 60% of the hemodialysis patients developed the same amount of antibodies as a placebo group of comparable patients (greater than or equal to 25 mU/ml), 78% of the renal transplant patients showed a 25% higher antibody concentration than a placebo group (half less than 25 mU/ml;half less than 50 mU/ml). According to these preliminary findings alpha-interferon may have an adjuvant effect on hepatitis B vaccination.

Effect of pindolol and propranolol on plasma renin and aldosterone in patients with renal allograft.

To investigate the effect of propranolol and pindolol on renin and aldosterone secretion, blood samples of 12 nephrectomized kidney transplant recipients were taken after 1 hour in supine position and 30 and 60 minutes after posture change. This procedure was repeated after 4 days under pindolol (3 X 5 mg/day) or propranolol (4 X 40 mg/day). Both pindolol and propranolol suppressed the significant orthostatic rise of plasma renin activity (PRA) seen without medication. Pindolol increased basal PRA markedly, whereas basal PRA under propranolol was the same as without betablockers. Plasma aldosterone (PA) showed significant orthostatic rise under all conditions and thus did not parallel PRA under betablockers. Suppression of PRA response to posture change by betablockers indicates that circulating catecholamines may be involved in orthostatic PRA regulation. The intrinsic sympathetic activity of pindolol results in an increase of basal PRA. In nephrectomized renal transplant recipients, postural PA changes do not seem to be triggered by PRA.

Immunogenicity of a hepatitis B subunit vaccine in hemodialysis and in renal transplant recipients.

A hepatitis B subunit vaccine was given to 59 medical staff members, 106 hemodialysis patients and 28 renal allograft recipients. The vaccine consisted of formalin-inactivated hepatitis Bsurface antigen (HBsAg) and was given in 3 doses (times 0, 1 and 6 months) of 20-40 micrograms. Some of the vaccinees received anti-HBs antibodies together with the first vaccine dose (active/passive vaccination). One month after the last infection, 93% of the medical staff members who had received active/passive immunisation and 97% of those who had received active immunisation had detectable anti-HBs antibodies with mean titers ranging from 1:512 to 1:1024. In the group of hemodialysis patients antibodies were detectable in 63-65% of the individuals who had received active or passive/active immunisation in mean titers between 1:32 and 1:64. Finally, only 32% of the renal allograft patients developed measurable anti-HBs antibodies, the titers of responders being still lower than in the hemodialysis patients. Side effects occurred following 10% of all vaccine injections and were always mild in nature. Within the 12 months observation period period following the first vaccination, 3 HBV events occurred in the 193 individuals: One aclinical case detected by a transient seroconversion against the hepatitis B core antigen, one anicteric and one icteric hepatitis case. The data illustrate the difficulties for active immunisation against hepatitis B of hemodialysis patients or of renal transplant recipients.