Von Hippel-Lindau disease: analysis of two families.

In this report we present two families with von Hippel-Lindau syndrome. We operated on haemangioblastomas in two members, one from each, in our clinic. In the first family we saw 17 lesions in 9 members. Although in the first family carcinoma of the kidney was often observed, in the second family retinal haemangioma was found to be predominant, namely, in eight out of nine patients. In both families there were 11 patients with retinal haemangioma; of these, 9 patients were blind (82%). In 6 patients with retinal haemangioblastoma blindness was unilateral and bilateral only in one. All the patients with renal carcinoma were male and died young. In one of our patients with renal carcinoma we found metastatic lesions in the distal and proximal parts of the femur, vertebral arch, cranium and the thoracic wall. In these two families 23 members had 32 lesions, from which eleven were retinal haemangiomas (3 + 8), nine haemangioblastomas of CNS (5 + 4), one a renal cyst (0 + 1), eight renal carcinomas (7 + 1), two pancreatic cysts (1 + 1) and one liver cyst (0 + 1).


[Chronic subdural hematoma as a cause for blindness].

The uncommon complication of bilateral blindness resulting from a decompressive neurosurgical procedure is presented by the case of a 51-year old patient suffering from a traumatic chronic subdural haematoma. A breakdown of the altered vasoregulation of the optic nerves due to papilledema at the time of intracranial pressure drop is supposed to be the etiological background of optic atrophy and consequent amaurosis. The causal relationship of accident trauma and blindness in the presented case is pointed out.


Glaucoma associated with epithelial downgrowth controlled with Molteno tube shunts.

We report two histopathologically proven cases of epithelial downgrowth in which the secondary glaucoma was controlled by a double-plate Molteno tube shunt and useful vision restored with a penetrating keratoplasty. The combination of a tube shunt and penetrating keratoplasty may be indicated to maintain useful vision in advanced cases of epithelial downgrowth associated with secondary glaucoma.


THC:YAG laser sclerostomy: the resident experience.

Retrospective review of 14 consecutive THC:YAG laser sclerostomies done without the use of anti-metabolites revealed a uniform closure of the filtering bleb within 6 months of follow up. Also, the sclerostomy site was closed by iris or fibrous tissue. Based on these findings, I recommend that the present THC:YAG laser sclerostomy protocol be altered to allow for antimetabolite usage, prevention and treatment of iris prolapse, and control of intraocular inflammation.


Anterior chamber tube shunt to an encircling band (Schocket procedure) in the treatment of refractory glaucoma.

We reviewed a series of 42 eyes in patients with refractory glaucoma who had undergone a Schocket procedure. The mean follow up was 17.5 months; the minimal follow up, 8 months. The success rate was 81%, with "success" defined as either (1) an intraocular pressure less than 21 and greater than 5 mm Hg, with a pressure reduction of at least 10%, and less or no medication; or (2) a pressure reduction of at least 30%, with no change of medication. When eyes with a loss of more then one Snellen line of visual acuity were interpreted as failures, the success rate dropped to 61%. Forty percent of all cases required revision. In four cases, the shunt had to be removed (three cases due to hypotony and one secondary to conjunctival erosion). These results are in the range of those obtained by other investigators using this technique or other tube-shunt procedures.


Intraocular lens insertion during vitrectomy.

Vitrectomy was performed in 10 patients in combination with posterior chamber intraocular lens (IOL) insertion. Indications for vitrectomy included traumatically dislocated cataract, choroidal hemorrhage, epiretinal membrane, lens involving intraocular foreign body, vitreous hemorrhage, and extruded anterior chamber IOL. Postoperative visual acuity improved in each case. The main advantages of simultaneous IOL insertion, in selected cases, are reduced cost and inconvenience, and more rapid visual rehabilitation.


Evaluation of silicone gel as a long-term vitreous substitute in non-human primates.

Two preparations of silicone gels were evaluated as long-term vitreous substitutes in the vitrectomized and lensectomized eyes of primates. Both preparations were injected in liquid form and polymerized in the vitreous cavity. There was no toxic effect on the ocular structures up to 13 months after implantation. Fundus examination and fluorescein angiography were possible through the less rigid gel, whereas the preparation with higher rigidity consistently appeared cloudy.


The wedge punctoplasty for treatment of punctal stenosis.

We describe a new instrument, the Reiss punctal punch, which is specifically designed to performa "wedge" punctoplasty. The Reiss punctal punch was used alone to treat three eyelids of three patients, and in conjunction with horizontal tightening of the eyelid to treat 35 eyelids of 18 patients with symptomatic epiphora related to punctal ectropion with secondary punctal stenosis. After a mean follow up of 12 months, 36/38 (95%) of the eyelids demonstrated a patent punctum, and symptomatic relief was achieved in 35/38 (92%) of the eyes.


YAG laser demonstration of the anatomy of the lens nucleus.

I used YAG laser energy to demonstrate the position and surface of the core of the lens nucleus and to prove the existence of the radial structure of the lens nucleus. Not only does hydrodissection of the epinuclear layers from the nuclear core demonstrate the existence of an anatomical substrate, but also radial fracturing of the nucleus both in phacoemulsification and planned extracapsular surgery can make use of these anatomical features to achieve smaller incisions and thereby smaller wounds.


Cyclodialysis cleft following holmium laser sclerostomy, treated by argon laser photocoagulation.

I report, to my knowledge for the first time, a case of inadvertent cyclodialysis cleft formation as a complication of holmium laser sclerostomy. Argon laser photocoagulation was used successfully to repair the cleft.


Ohmmeter-guided nasolacrimal intubation.

Retrieval of steel probes via the inferior meatus of the nose in monocanalicular and bicanalicular nasolacrimal intubation can be a tricky maneuver, possibly complicated by bleeding from lacerated soft tissue around the inferior turbinate. Using a low-voltage device (essentially, an ohmmeter) to assure contact between the retrieval hook and the distal end of the steel probe greatly facilitates the procedure.


Treatment of scleromalacia perforans with dura mater grafting.

We describe, to our knowledge for the first time in the English literature, the successful use of cadaveric dura mater in reinforcing the sclera in a rheumatoid arthritis patient with scleromalacia perforans.


Lack of toxicity of intravitreally administered interferon alpha-2a.

We investigated the toxicity of single doses of intravitreally administered interferon alpha-2a in albino rabbits. Following injection of interferon in doses of 40,000, 80,000, 160,000, 320,000, and 640,000 IU/0.1 mL, no significant histologic changes were detected by light and electron microscopy. Photopic and scotopic electroretinography showed no alteration of retinal function.


A superior and inferior orbital rim-based exophthalmometer (orbitometer).

In exophthalmometry when the lateral orbital rim is used as the instrument's fixation base, any alteration in the rim will render serial measurements inaccurate. The exophthalmometer we describe (technically, an "orbitometer") uses the superior and inferior orbital rim areas as a base of reference, making it particularly useful in lateral orbitotomy procedures. This instrument can be aligned at the midpupil horizontally and vertically with a vertical fixation bar. In addition, a vertical bar gradient scale allows measurement of hypoophthalmos and hyperophthalmos.


A new endoscope for ophthalmic microsurgery.

We present an endoscope designed for ophthalmic microsurgery. The handpiece contains a charge-coupled device, a solid-state imager (250,000 pixels), and a probe (either 0.89 or 1.5 mm in diameter), including the light guide. The light source is a halogen lamp. The clear views the instrument provides of the ciliary sulcus and ciliary body behind the iris make it useful in secondary posterior chamber intraocular lens implantation using the ciliary sulcus suturing technique, and in endolaser photocoagulation of the ciliary body in end-stage glaucoma. It also is useful in performing vitrectomy in cases in which visualization is difficult because of corneal opacification or fluid-gas exchange.


Associations between microbial species in dental root canal infections.

The existence of commensal or antagonistic relationships between microorganisms in the root canals of teeth with apical periodontitis was investigated. Samples were taken from 65 infected human root canals and were analysed according to species, frequency of occurrence and proportion of the total isolated flora. The most frequent species were Fusobacterium nucleatum, Prevotella intermedia, Peptostreptococcus micros, Peptostreptococcus anaerobius, Eubacterium alactolyticum, Eubacterium lentum and Wolinella recta. An odds ratio system was used to calculate positive or negative associations between the isolated bacteria. Strong positive associations were found between F. nucleatum and P. micros, Porphyromonas endodontalis, Selenomonas sputigena and W. recta. There was also a positive association between P. intermedia and P. micros, P. anaerobius and the eubacteria. In general, species of streptococci, Propionibacterium propionica, Capnocytophaga ochracea and Veillonella parvula showed no or negative associations with the other bacteria. The results are consistent with the concept of a special and selective environment occurring in the root canal that is due, in part, to the cooperative as well as antagonistic nature of the relationships between bacteria in the root canal.


The age-dependence of bacterial presence on oral epithelial surfaces in vivo.

Epithelial cells obtained by gentle scraping with a brush tip from the gingival margin of d 11 or 51, adjacent labial mucosa and buccal mucosa of children, adolescents and adults were stained with acridine orange and examined under a fluorescence microscope. The amount of bacteria appearing on the epithelial cells was assessed and the form of the adhered bacteria was evaluated. An age-related descending trend (negative Pearson's r in all sites) could be seen in the number of colonized cells (> 50 bacteria present) in gingival, labial and buccal areas. Adolescents and adults had significantly fewer epithelial cells with colonization of bacteria in the labial and buccal areas compared with children under 6 years. Only cocciformed bacteria were seen associated with the epithelial cells. By studying bacterial adhesion according to methods outlined in the present study, it should be possible to more closely investigate the bacteria-host relationships as they appear in nature.


Periodontal pathogens in the shallow pockets of immigrants from developing countries.

The aim of this study was to examine the distribution of typical periodontitis-associated microorganisms in refugees arriving from non-industrialized countries, and to relate the presence of these organisms to the periodontal condition of the subjects. Thirty males between 35-44 years of age were surveyed. Dental plaque, calculus, gingivitis, loss of attachment, and probing depths were recorded for all surfaces. A total of 90 microbiological samples were taken with paper points from mesial sites of teeth 16, 36 and 41. Microbiological test sites were grouped by probing depths and loss of attachment. Only 16.8% of all surfaces had probing depths > 3 mm, although 90.7% of surfaces had loss of attachment > 1 mm. Twenty-one sites with obvious periodontal destruction (PD > 3 mm, LA > 2 mm) showed the greatest recovery of Porphyromonas gingivalis (66.7%). However, 51 sites with minimal periodontal disease (PD < or = 3 mm, LA < 2 mm) and with no gingival recession also showed a relatively high detection frequency of P. gingivalis (34.1%). Twenty-four of these samples came from 12 patients with no pockets > 5 mm and with less than 10% of all sites yielding pockets > 3 mm. The detection frequencies of Prevotella intermedia (91.6%), Bacteroides forsythus (25.0%), Wolinella spp. (33.3%) and Actinobacillus actinomycetemcomitans (50.0%) were similar in these sites compared with periodontitis sites. Morphologically distinct isolates, from 19 individuals positive for A. actinomycetemcomitans, were serotyped by indirect immunofluorescence.(ABSTRACT TRUNCATED AT 250 WORDS)


Relationship between oral gram-negative anaerobic bacteria in saliva of the mother and the colonization of her edentulous infant.

Various gram-negative anaerobic bacterial species can be detected in the oral flora of edentulous infants. However, knowledge of the initial infection source is still scarce. Thirty Caucasian mothers (mean age 30 years) and their edentulous infants (mean age 3 months) were examined for the possible similarity of the oral gram-negative anaerobic flora. Paraffin-stimulated saliva was collected from the mothers. A pooled swab sample from mucosal surfaces and unstimulated saliva were collected from the infants. The samples were inoculated on nonselective and selective media and cultured aerobically and anaerobically. All of the 30 mothers harbored Fusobacterium nucleatum and 29 mothers Prevotella melaninogenica in their saliva. The salivary levels of P. melaninogenica, F. nucleatum, nonpigmented Prevotella spp., Prevotella intermedia and Prevotella loescheii exceeded 10(4) CFU/ml in about half of the 30 mothers. At this maternal salivary level, the infants' colonization frequency of P. melaninogenica and F. nucleatum was doubled. A positive correlation between maternal salivary concentration and infant's colonization was found for P. melaninogenica. No positive association was found with nonpigmented Prevotella spp., P. intermedia and P. loescheii. It can be speculated that maternal saliva may act as a source of some gram-negative anaerobes in the oral microflora of edentulous infants as early as before tooth eruption.


Frequency and stability of mono- or poly-infection by Actinobacillus actinomycetemcomitans serotypes a, b, c, d or e.

The aims of the study were to determine the prevalence of simultaneously multiple Actinobacillus actinomycetemcomitans serotypes in one individual, stability of infection by the same serotype and the occurrence of previously not described serotypes of A. actinomycetemcomitans. The serotypes of 515 clinical isolates of A. actinomycetemcomitans from 91 Finnish, Caucasian subjects, including 321 follow-up samples from 51 subjects, were determined with immunodiffusion assay. Most subjects (n = 86, 95%) were infected with one serotype only; 466 (91%) isolates from 80 subjects belonged to serotype a (25% of isolates/25 subjects), b (25% of isolates/27 subjects) or c (41% of isolates/30 subjects). Fifteen isolates from 4 subjects reacted with the antiserum raised against previously untypable clinical strain IDH 781 (serotype d) and 18 isolates from 5 subjects with the antiserum raised against strain IDH 1705 or IDH 3096 (serotype e). Sixteen (3%) isolates from 5 subjects remained untypable. The same infecting A. actinomycetemcomitans serotype(s) persisted for the 1-6 years of follow-up. In conclusion, the study indicates a rare simultaneous occurrence of multiple oral A. actinomycetemcomitans serotypes, the stability of infection by the same serotype(s) and the existence of serotypes of A. actinomycetemcomitans not previously described.


Coaggregation studies of the Eubacterium species.

Eubacterium species are gram-positive anaerobic rods that are frequently isolated from subgingival plaque of periodontal pockets. Five Eubacterium species were tested for their ability to coaggregate with 33 oral bacterial strains. Using visual and turbidimetric assays, coaggregation was observed among Eubacterium brachy, Eubacterium nodatum, Eubacterium alactolyticum and Eubacterium limosum strains only when tested with Fusobacterium nucleatum strains; Eubacterium saburreum displayed only weak coaggregation ability. Coaggregation between F. nucleatum and the Eubacterium species was observed over a wide range of concentrations of each organism. The F. nucleatum strains contained a heat labile and the Eubacterium species a heat stabile coaggregation receptor. Arginine, histidine, lysine and glycine inhibited the coaggregation between F. nucleatum and the Eubacterium species. Sugars and other amino acids tested did not inhibit the observed coaggregation. Rabbit anti-F. nucleatum serum completely inhibited coaggregation, but anti-E. brachy serum and normal rabbit serum did not. As these anaerobic microorganisms are frequently isolated from the same oral lesions, the surface interactions observed may be important in the pathogenesis of these polymicrobic infections.


Characterization of shared antigens of Fusobacterium nucleatum and Fusobacterium necrophorum.

Fusobacterium nucleatum and Fusobacterium necrophorum are gram-negative, non-spore-forming anaerobic rods, frequently isolated from the normal flora and diseased lesions of the human oral cavity, gastrointestinal and genitourinary tracts. F. necrophorum is also known to be an animal pathogen. Studies were undertaken with rabbit anti-F. nucleatum sera and with human adult periodontitis (AP) sera that demonstrated the sharing of antigens between the two species. Immunodiffusion and immunoelectrophoresis studies of Fusobacterium species with rabbit anti-F. nucleatum sera demonstrated the presence of shared antigen(s) between F. nucleatum and F. necrophorum. Adsorption studies of AP sera in an enzyme-linked immunosorbent assay demonstrated the presence of antibodies reacting with the shared antigens of the two species. Immunoblot (IB) analysis of a soluble protein preparation of the two species of Fusobacterium, when allowed to react with rabbit anti-F. nucleatum 10197 serum, demonstrated 53 kDa and 30 kDa bands present in members of the two species. Further, IB analysis of protein preparations of the two species with AP sera indicated the presence of antibodies reacting with the shared 53 kDa band and in some cases the 30 kDa band. During serological testing with antisera or host immune studies with human sera to these species, the presence of shared antigens must be considered.


The breakdown and utilization of peptides by strains of Fusobacterium nucleatum.

It has been claimed that most strains of Fusobacterium nucleatum require peptides rather than free amino acids for growth. In contrast, we have shown that, under continuous culture conditions, all strains tested grow in a chemically defined medium (CDM). The purposes of this study were to determine whether resting cells of F. nucleatum could attack unsubstituted peptides and whether growing cells could utilize a peptide fraction prepared from a commercial peptone. Resting cells cleaved all 19 peptides, containing 3-6 residues, and the 4 key energy-yielding amino acids--Glu, His, Ser and Lys--were rapidly taken up. A hydrophilic Casitone fraction, rich in Glu, promoted growth and peptides < 1 kDa were rapidly utilized. The cleaved residues metabolized were those previously shown to limit growth in CDM: Glu, Ser, His and Lys. The endopeptidase activities of Porphyromonas gingivalis would provide the necessary peptides for the growth of F. nucleatum, which may partly explain why these two organisms frequently coexist in periodontally diseased sites.


Acid production by streptococci growing at low pH in a chemostat under anaerobic conditions.

Streptococcus mutans and other oral streptococci were grown in continuous culture under strictly anaerobic conditions. When the cultural pH was kept at 7.0, the main acid products were formate and acetate, as reported previously. However, more lactate was produced at pH values of 5.5 or 6.0, with a concomitant decrease in formate and acetate production. This change in fermentation products could partly be ascribed to a change in intracellular pH and difference in the pH optima between pyruvate formate-lyase (PFL) and lactate dehydrogenase (LDH). At extracellular pH values of 7.0 and 5.5, the intracellular pH values of S. mutans NCIB 11723 were 7.5 and 6.6, respectively. The pH optima of PFL and LDH were 7.8 and 5.5-6.3, respectively. The cells had also a larger amount of LDH during growth at pH 5.5 than at pH 7.0.


Reduced nicotinamide adenine dinucleotide oxidase involvement in defense against oxygen toxicity of Streptococcus mutans.

The growth inhibition of the Streptococcus mutans group, including Streptococcus mutans, Streptococcus cricetus, Streptococcus rattus and Streptococcus sobrinus, on glucose by oxygen and the properties of reduced nicotinamide adenine dinucleotide (NADH) oxidase induced by oxygen, using a representative oxygen-tolerant strain, were examined. The growth response to oxygen varied among strains and correlated with the level of NADH oxidase activity in the cell extract. The induced synthesis of NADH oxidase as well as superoxide dismutase was affected by oxygen tension and energy sources. The induced NADH oxidase involved at least two types, major H2O-forming NADH oxidase and minor H2O2-forming NADH oxidase activity. In the presence of a scavenger of H2O2, pyruvate, the growth inhibition by oxygen in an oxygen-sensitive strain (GS5) was protected but not in another oxygen-sensitive strain (MT8148). The high level of induced H2O-forming NADH oxidase activity protected against oxygen toxicity.


Inhibition of Candida albicans by the Peroxidase/SCN-/H2O2 system.

Effects of the salivary peroxidase (SPO) system on the growth, glucose uptake and metabolic activities of oral bacteria are well documented but the effects on oral fungi are virtually unknown. Therefore, the viability of Candida albicans (ATCC 28366) exposed to the peroxidase/SCN-/H2O2 system was studied in sterilized saliva, in phosphate-buffered saline (PBS) and in potassium chloride. The growth of C. albicans in glucose-supplemented saliva was faster at pH 5.5 than at pH 7. The addition of the complete SPO (or lactoperoxidase) system to either sterilized saliva, KCl (50 microM) or PBS at pH 5.5 inhibited dose-dependently the viability of C. albicans in KCl, but no inhibition was found in PBS or saliva. Maximal inhibition was achieved in 2 h and with > 320 microM of peroxidase-generated HOSCN/OSCN-. However, physiological salivary concentrations of phosphate (> or = 1.0 mM) and PBS blocked the antifungal effect of HOSCN/OSCN-. The relative proportions of SCN- and H2O2 were critical to the antifungal effects. With 0.2 mM KSCN, a complete loss of viability was achieved, though the HOSCN/OSCN- concentrations did not exceed 100 microM. It is concluded that C. albicans is sensitive to HOSCN/OSCN- but salivary concentrations of phosphate block the antifungal effect of the peroxidase systems.


Characterization of two platelet aggregation inhibitor-like polypeptides from viper venom.

Two polypeptides, eristocophins I and II, have been characterized from leaf-nosed viper (Eristocophis macmahoni) venom. They contain 10 half-Cys residues of a total of 61/62 residues, have 72% residue identity, and exhibit similarities to platelet aggregation inhibitors and segments of adhesive proteins. Eristocophin I contains the sequence Arg-Gly-Asp, known to inhibit fibrinogen interaction with the platelet receptor. Eristocophin II has Met instead of Arg in this sequence, and an adjacent Trp-Asn-Asp segment. The latter is also typical of adhesive proteins, thus linking two potentially functional segments in one molecule. Exchanges are maximal in these segments, suggesting that the polypeptides exhibit functional divergence with isoform differences in important regions.


A sensitive and specific two-site, sandwich-amplified enzyme immunoassay for neuropeptide Y.

The development of a new enzyme immunoassay for neuropeptide Y (NPY) is reported. Two monoclonal antibodies directed against distinct epitopes of NPY are used, one as a capture antibody (NPY02) and the other one as an indicator antibody (NPY05), this latter antibody being labeled with alkaline phosphatase. The assay calibration curve was performed over concentrations of 1 to 250 pM in a NPY-free plasma. The intra-assay coefficient of variation (CV) ranged from 0.025 to 11.9%, whereas the interassay CV was comprised between 5 and 12%. The limit of detection of this assay was 1 pM (100 amol/well). Neuropeptide Y levels are related to sampling conditions; basal concentrations of NPY with low SEM are found when less than 1.2 ml of blood is taken in EDTA tubes, the sample is centrifuged at 4 degrees C, and immediately frozen. Unanesthetized spontaneously hypertensive rats exhibited higher NPY plasma concentrations than normotensive Wistar-Kyoto controls (53 +/- 7 pM and 25 +/- 2 pM, respectively, mean +/- SEM, p < 0.01). Plasma NPY levels are similar in 16- and 36-week-old animals. In conclusion, this technique makes it possible to assay a large number of samples within 24 h without requiring radioactivity.


Effects of thermal peptides on retention of footshock avoidance training in mice.

Some hydrophobic polypeptides known as thermal proteins have been found to have neurotrophic effects. Thermal proteins were synthesized from aspartic acid, glutamic acid, proline, and tryptophan. Two hydrophobic and one nonhydrophobic polymers were injected intracerebroventricularly into brains of mice after partial training on footshock avoidance run in a T-maze. When retention was tested 1 week later, the hydrophobic polymers enhanced retention while the nonhydrophobic polymer did not. Thermal proteins exhibiting hydrophobicity and having neurotrophic effects may aid in altering synaptic connections by facilitating cell recognition.


Oxytocin in obsessive compulsive disorder.

A double-blind, placebo-controlled study with syntocinon (oxytocin) was carried out in 12 patients, nine females and three males with obsessive compulsive disorder (OCD). Patients were treated by intranasal administration of oxytocin spray (18 IU per day) or placebo. No reductions in the number of obsessions or compulsive behaviors were observed in either treatment group. To evaluate whether a higher dosage would exert more beneficial effects, two additional patients were treated with a threefold higher dosage of oxytocin using an open design. In one patient a slight reduction in the number of checking rituals was observed, whereas in the other patient virtually no effect was observed. The results of this study do not support the hypothesis that oxytocin might be a potential anticompulsive agent.


Isolation and quantitation of several new peptides from the canine neurotensin/neuromedin N precursor.

Using antisera towards the bioactive peptides, neurotensin and neuromedin N, as well as towards the N-terminal and C-terminal regions of their shared 170-residue precursor, peptides representing various portions of the precursor were isolated from extracts of canine ileum. In total, seven peptides were isolated, two of which had not been previously identified. One was the C-terminal tail of the precursor (Gly-Ser-Tyr-Tyr-Tyr) and the other was the tail peptide extended N-terminally to include neurotensin (Glp-Leu-Tyr-Glu-Asn-Lys-Pro-Arg-Arg-Pro-Tyr-Ile-Leu-Lys-Arg-Gly-Ser-Tyr -Tyr- Tyr). By comparing the measured concentrations for each of the identified peptides, it was established that processing at the three Lys-Arg cleavage sites within the precursor did not occur to the same extent. Cleavage at the N-terminus of neuromedin N was approximately 10% complete, that between neurotensin and the tail was approximately 90% complete, and that between neuromedin N and neurotensin was approximately 95% complete. Three immunoreactive proteins were also identified by immunochemical and chromatographic analyses: N-terminally extended neuromedin N (125 residues), N-terminally extended neurotensin (140 residues), and the entire 147-residue precursor. It was concluded that neurotensin, tail and large molecular neuromedin N were the primary products of processing for this precursor in canine ileum, while minor products included neuromedin N, neurotensin tail, and large molecular neurotensin.


Calcium-dependent pro-cholecystokinin V-9-M immunoreactive peptide release from rat brain slices and CCK-secreting rat medullary thyroid carcinoma cells in culture.

The release of peptides immunoreactive for a synthetic peptide (V-9-M) contained in the amino-terminal of pro-CCK was examined. The potassium-evoked release of V-9-M immunoreactive peptides from rat cerebral cortical slices in vitro was calcium dependent. Cholecystokinin-secreting rat medullary thyroid carcinoma cells also secreted significant quantities of these peptides. Sephadex column chromatography of the release media from slices and cells showed two V-9-M immunoreactive peptides, one larger and one smaller than V-9-M itself. Previous behavioral studies have suggested that V-9-M has a distinct neuropharmacological profile. These results demonstrate that V-9-M-like peptides are released along with CCK-8 and are consistent with the hypothesis that V-9-M-like peptides may be neurotransmitters or neuromodulators or may be involved in the sorting or transport of CCK-8.


D-amino acid and alanine scans of the bioactive portion of porcine motilin.

A recent systematic study of porcine motilin fragments has clearly shown that biological activity resides in the amino-terminal end. The amino-terminal tetradecapeptide retains more than 90% of the potency of the full molecule. We now examined the effect of replacement of residues 1 through 11 by either their D-isomer or by alanine in [Leu13]pMOT(1-14). Peptides were synthesized using Fmoc solid phase methodology, purified by HPLC, and assayed for their ability to displace bound motilin (rabbit antral smooth muscle homogenate) and to induce contractions (isolated rabbit duodenal segments). The negative logarithm of the concentration displacing 50% of the tracer (pIC50), or producing 50% of the maximal contractile response (pEC50), was determined. All compounds were still full agonists. A reduction in potency of more than two log units was seen for the compounds in which residues 1 (Phe), 4 (Ile), and 7 (Tyr) were replaced by Ala and residues 3 (Pro), 4 (Ile), and 6 (Thr) by their D-isomer. The largest drop was noted for the analogs substituted at position 4. For all compounds there was an almost perfect correlation between the pIC50 and the pEC50 values (r = 0.96), although the pEC50 was consistently smaller. These results show that the biological activity of motilin is mainly determined by the first seven residues. The pharmacophore consists of the aromatic rings from Phe1 and Tyr7 and the aliphatic side chains from Val2 and Ile4. Pro3, Phe5, and Thr6 may stabilize the bioactive conformation.


Pituitary adenylate cyclase activating polypeptide (PACAP) reduces food intake in mice.

Pituitary adenylate cyclase activating peptide (PACAP) is a peptide that is present in the hypothalamus and other areas of the rat brain. This study demonstrates that PACAP reduces food intake after intracerebroventricular injection in food-deprived mice. Behavioral analysis suggests that this decrease in food intake is, in part, compensated for by an increase in other behaviors. Pituitary adenylate cyclase activating peptide also was demonstrated to antagonize increased food intake resulting from administration of neuropeptide Y. Thus, PACAP joins a growing list of neuropeptides involved in the central regulation of food intake.


Large and prolonged in vivo response of pancreatic secretion to phenylethylamide and phenylethylester derivatives of Boc-[Nle28-Nle31]CCK(26-33) in the rat.

Supramaximal doses of cholecystokinin (CCK) induce in vitro submaximal biological responses (i.e., smaller by 50% than the response to a maximal dose of CCK), desensitization and residual stimulation, and in vivo secretory inhibition and edematous pancreatitis. It has been reported previously that supramaximal doses of Boc-[Nle28-Nle31]CCK(27-32)/- phenylethylester (JMV 180) do not produce these effects. The aim of this study was to analyze the in vivo response of pancreatic secretion of the rat to a wide dose range of Boc-[Nle28-Nle31]CCK(26-33) (JMV118), an analog of CCK8 with the same activity spectrum as CCK8, to JMV180 and to Boc-[Nle28-Nle31]CCK(27-32)-phenylethylamide (JMV170). The three peptides were administered as intravenous infusions and as bolus intravenous injections. In the case of infusions, the same maximal effect was observed with all three peptides. It was obtained with 22.5 pmol/kg.min of JMV118; JMV180 and JMV170 were about 700 times less potent. In the case of bolus injections, the maximal response to JMV118 was observed with 450 pmol/kg, and the response peaked 10-15 min after the injection. Higher doses of JMV118 induced a secretory peak that was smaller and delayed relative to the moment of injection. JMV180 and JMV170 were about 500 times less potent: the maximal response was observed with 218700 pmol/kg and peaked 10-15 min after the injection. Larger doses of JMV180 and JMV170 produced neither supramaximal inhibition nor a delayed peak response, but induced a sustained stimulation of pancreatic secretion that could last more than 3 h after the injection.(ABSTRACT TRUNCATED AT 250 WORDS)


The role of cholecystokinin (CCK8) on glucose production and elimination, and on plasma insulin and glucose in rats.

The effects of the gastrointestinal hormone and neurotransmitter cholecystokinin (CCK8) are complex, since it exhibits both an insulinotropic and a glucagonotropic effect. We investigated CCK8 in vivo with respect to glucose fluxes (production and elimination) at both low (6 mM) and high plasma glucose levels (9 mM) using the primed constant D-[3-3H]glucose infusion technique. In the presence of high glucose levels there was a dose-dependent increase in glucose elimination by CCK8. No effect of CCK8 on glucose production at a high glucose infusion rate (500 mg/kg per h) was observed in contrast to a low glucose infusion rate (100 mg/kg per h); plasma glucagon levels were elevated. All effects on glucose production and elimination were specific, since they were abolished by the CCK receptor antagonist L-364,718. In summary, glucose elimination was slightly increased by CCK8 at low glucose levels but increased to a greater extent at high glucose levels; glucose production was increased by CCK8 only at low glucose levels. Thus, CCK is a regulator of glucose homeostasis.


Peripheral insulin administration attenuates the increase in neuropeptide Y concentrations in the hypothalamic arcuate nucleus of fasted rats.

Fasting increases neuropeptide Y (NPY) concentrations in the arcuate nucleus (ARC), its site of synthesis, and in other regions of the rat hypothalamus. Neuropeptide Y is a potent central orexigenic agent and may therefore stimulate appetite during fasting. We tested the hypothesis that low plasma insulin levels stimulate ARC levels of NPY in fasted rats. Compared with freely fed controls (n = 8), rats fasted for 72 h (n = 8) showed significantly lower plasma insulin levels (28.9 +/- 1.6 vs. 52.6 +/- 5.7 pmol/l; p < 0.001) and higher ARC NPY concentrations (14.2 +/- 1.8 vs. 8.4 +/- 2.2 fmol/micrograms protein; p < 0.001). Fasted rats treated with subcutaneous insulin (5 U/kg/day; n = 10), which nearly normalized plasma insulin (46.6 +/- 2.8 pmol/l), showed intermediate ARC NPY levels (11.2 +/- 1.4 fmol/micrograms protein; p < 0.01 vs. controls and untreated fasted rats). Insulin administered peripherally, therefore, attenuates fasting-induced NPY increases in the ARC, supporting the hypothesis that hypoinsulinemia stimulates hypothalamic NPY.


The effect of N-terminal substitutions on the biological activity of MSH fragments.

In order to study the role of N-terminal substitutions of peptide sequences related to the active site of alpha-melanotropin, [Glp5]alpha-MSH(5-10), [Glp5,D-Phe7]alpha-MSH(5-10), [Sar5,D-Phe7]alpha-MSH(5-10), [Nle4,D-Phe7]alpha-MSH(4-10), [N-carbamoyl]alpha-MSH(5-10), and formyl and acetyl derivatives of alpha-MSH(5-10), [Gly5]alpha-MSH(5-10) and [Gly5,D-Phe7]alpha-MSH(5-10), were synthesized in solution. The N-terminal acylations enhance by 2 to 10 times the melanin-dispersing activity of the unsubstituted sequences. Alkylation of the N-terminus does not change the biological activity of the parent peptide, suggesting the necessity of a carbonyl group for increasing the hormonal effect.


Rainbow trout (Oncorhynchus mykiss) neuropeptide Y.

Neuropeptide Y (NPY) has been isolated from brain extracts of the rainbow trout (Oncorhynchus mykiss) and subjected to structural analyses. Plasma desorption mass spectroscopy estimated the molecular mass of the purified peptide as 4303.9 Da. Automated Edman degradation unequivocally established the sequence of a 36 amino acid residue peptide as: Tyr-Pro-Pro-Lys-Pro-Glu-Asn-Pro-Gly-Glu-Asp-Ala-Pro-Pro-Glu-Glu-Leu-Ala- Lys- Tyr-Tyr-Thr-Ala-Leu-Arg-His-Tyr-Ile-Asn-Leu-Ile-Thr-Arg-Gln-Arg-Tyr. The molecular mass calculated from this sequence (4304 Da) is consistent with that obtained by mass spectroscopy. The presence of a C-terminal amide was established by radioimmunoassay. Rainbow trout NPY is identical in primary structure to coho salmon (Oncorhynchus kisutch) pancreatic polypeptide (PP). These data may indicate that, in this group of salmonid fishes, a single member of the NPY/PP peptide family is expressed in both neurons and peripheral endocrine cells.


The effect of corticotropin-releasing factor (CRF) on autonomic and behavioral responses during shock-prod burying test in rats.

When administered intracerebroventricularly (ICV) in rats, corticotropin-releasing factor (CRF) possesses arousing and anxiogenic properties, which may be found reflected in autonomic and behavioral activation. As these responses are dependent on dose and situation, ICV-injected CRF may affect behavioral responses to a defined stimulus in a different fashion than autonomic concomitants. Two experiments were conducted in order to test this hypothesis. In both experiments, rats were treated ICV with CRF or an artificial cerebrospinal fluid (aCSF) 5 min prior to a 15-min exposure to an electrified prod (shock-prod burying test, SPB test) in their home cages. In the first experiment, 0.3 ng CRF injected ICV in unhandled rats significantly reduced the prod-burying response to electric shock, in favor of immobility, whereas following 300 ng CRF ICV, the predominant behavioral response was grooming behavior. In contrast, habituated rats, implanted with telemetric devices to measure heart rate, core temperature, and gross activity in the second experiment, showed a significant increase of burying behavior after 0.3 ng CRF ICV, in comparison to vehicle-treated controls. However, simultaneous cardiac acceleration was of the same magnitude and duration in both groups. In addition, whereas similar rises in CT were observed in both groups during the SPB test, CRF-treated rats showed more marked rise in core temperature during the first 15 min of the posttest period. At the 24-h retention test, rats belonging to the CRF group showed burying behavior and HR responses, in onset, magnitude, and duration similar to day 1, whereas extinction of the burying response and tachycardia was found in controls. Changes in CT, although less marked, showed the same pattern as on day 1 in both groups. These results show a differential effect of central CRF on behavioral and autonomic activation induced by a well-defined stressful stimulus. The response to CRF seems to be not only situation related, but also dependent on the pretest experience of the animal.


Microvascular effects of atrial natriuretic peptide in rat cremaster.

Experiments utilized the open cremaster preparation to test the hypothesis that atrial natriuretic peptide (ANP)-induced volume changes result from microvascular resistance alterations. Atrial natriuretic peptide (25, 100, and 500 ng/kg/min, IV) or vehicle was infused into anesthetized rats. At the two highest ANP infusion rates, mean arterial pressure was significantly reduced from 104 +/- 3 (control) to 87 +/- 2 and 77 +/- 2 mmHg, respectively. Hematocrit was 41.0 +/- 0.8 and 45.6 +/- 0.9% (p < 0.05) at the end of vehicle and ANP infusions, respectively. Despite these effects of ANP, there were no significant arteriolar or venular diameter alterations. Thirty microM nitroprusside significantly dilated all vessel segments except large venules. These observations suggest that resistance alterations in the skeletal muscle microvasculature are not the cause of ANP-induced fluid movement.


Characterization of endozepine-related peptides in the central nervous system and in peripheral tissues of the rat.

Endozepines represent a novel family of regulatory peptides that have been isolated by their ability to displace benzodiazepines from their binding sites. All endozepines derive from an 86 amino acid precursor polypeptide called diazepam binding inhibitor (DBI), which generates, through proteolytic cleavage, several biologically active endozepines. The aim of the present study was to compare the molecular forms of endozepines present in different regions of the rat brain and in various peripheral organs using an antiserum raised against the central (biologically active) region of DBI. Combination of HPLC analysis and RIA detection revealed the existence of two major forms (peaks I and II) of endozepine-immunoreactive peptides. The retention times of the two peaks (36 and 39 min, respectively) were identical in all tissues or organs tested. Western blotting analysis of cerebral cortex extracts confirmed the existence of two immunoreactive species with apparent molecular weights 4000 and 6000 Da, which respectively correspond to peaks I and II. Tryptic digestion of peaks I and II generated a single immunoreactive peptide that coeluted with the synthetic octadecaneuropeptide ODN [DBI(33-50)]. These results show that, in different parts of the brain and in various peripheral organs, DBI is rapidly processed to generate two peptides of apparent molecular weight of 4000 and 6000 Da, which both possess the biologically active determinant of endozepines.


Immunosuppressive activity of antamanide and some of its analogues.

In connection with our discovery of a strong immunosuppressive activity of cyclolinopeptide A (CLA), we investigated immunosuppressive properties of antamanide and a number of its analogues, including symmetrical antamanide, and compared them with the activities of cyclosporin A and CLA. The peptides were investigated by using plaque forming cell (PFC), graft-versus-host (GvH), delayed type hypersensitivity (DTH), and autologous rosette formation cell (ARFC) tests. Antamanide and symmetrical antamanide exhibit an immunosuppressive activity lower than CLA. Linear antamanide fragments are also active. At higher concentrations of the latter peptides, toxic effects occur.


Pyrexia of unknown origin: changing spectrum of diseases in two consecutive series.

Comparison was made of the aetiology and methods of diagnosis in two series of patients meeting the classic criteria of pyrexia of unknown origin during 1968-1981 and during 1982-1989 seen in the Department of Internal Medicine at La Paz University Hospital, Madrid, Spain. There was a statistically significant decrease in the percentage of infections and an increase in neoplasms and connective tissue disorders in the second series. The percentage of patients diagnosed by laparatomy was similar in both series but the diagnosis yield at laparotomy was greater in the second period. Pyrexia of unknown origin continues to be a condition which can defy clinical expertise in in spite of advances in diagnostic techniques.


The effect of hemiplegia on blood pressure measurement in the elderly.

The blood pressure in both arms of 103 unselected hemiplegic patients was measured using a random-zero sphygmomanometer. Although for the whole sample the mean blood pressure in the paretic and unaffected arm was similar, a significant difference was found when the patients were subdivided according to the tone of the arm. The blood pressure was higher in paretic arms of patients with a spastic stroke and lower in the affected arm if the tone was flaccid. No other characteristics were associated with significant blood pressure differences, so that the findings appear to be directly related to changes in muscle tone. After a stroke the blood pressure should always be measured in the unaffected arm because changes in tone make measurements unreliable.


Decreased behavioral effects of daily intracerebroventricular bombesin.

Intracerebroventricular (ICV) bombesin increases grooming and decreases food intake in rats. We examined tolerance to these effects by administering a daily injection of either saline or 25 ng bombesin to rats for 8 days via lateral ventricular cannulas. Food intake and grooming were monitored. After 8 days bombesin no longer increased grooming or decreased food intake in bombesin-treated rats, but did increase grooming and decrease food intake in saline-treated rats. This development of behavioral tolerance conflicts with previous reports using larger doses and demonstrates that repeated small doses of ICV bombesin produce different effects from larger doses.


Endogenous opiates: 1991.

This paper is the fourteenth installment of our annual review of research concerning the opiate system. It includes papers published during 1991 involving the behavioral, nonanalgesic, effects of the endogenous opiate peptides. The specific topics this year include stress; tolerance and dependence; eating; drinking; gastrointestinal and renal function; mental illness and mood; learning, memory, and reward; cardiovascular responses; respiration and thermoregulation; seizures and other neurological disorders; electrical-related activity; general activity and locomotion; sex, pregnancy, and development; immunological responses; and other behaviors.


Mycobacteria as a cause of infective exacerbation in bronchiectasis.

In 91 patients with bronchiectasis seen over 6 years, a positive mycobacterial culture was obtained in 12 cases (13%). The organisms isolated were Mycobacterium tuberculosis in nine cases, Mycobacterium avium in two cases and Mycobacterium tuberculosis and chelonei were obtained on separate occasions in one case. Computed tomography and/or bronchography showed that the bronchiectatic changes commonly involved the lower lobes and to a lesser extent, the middle and lingula lobes. In none of these 12 cases was tuberculosis strongly suspected on clinical or radiological grounds. We conclude that mycobacterial infections are common in patients with bronchiectasis and sputum should be cultured for mycobacteria periodically in these patients. In doubtful cases, bronchoscopy may be helpful to obtain a positive mycobacterial culture.


CGRP immunoreactivity and NADPH-diaphorase in afferent nerves of the rat penis.

Calcitonin gene-related peptide (CGRP)-immunoreactive afferent nerve fibers are abundant in the rat penis. In addition, NADPH-diaphorase, which stains for nitric oxide synthase, has been localized within both autonomic and sensory dorsal root ganglia (DRG) and may be part of an important biochemical pathway involved in penile tumescence. The purpose of this study was: 1) to examine the circuitry of afferent nerves that are CGRP immunoreactive from the L6 DRG, 2) to examine the possibility that there are NADPH-diaphorase-positive afferent fibers from the L6 DRG to the rat penis, and 3) to examine the localization and colocalization of CGRP and NADPH-diaphorase within L6 DRG afferent perikarya. Calcitonin gene-related peptide immunostaining in the penis was eliminated following a bilateral transection of the pudendal nerves, but was unchanged following a bilateral transection of the pelvic splanchnic or hypogastric nerves. The NADPH-diaphorase staining was not altered by any of the nerve transections. Injection of the retrograde axonal tracer fluorogold (FG) into the dorsum penis labeled perikarya in the L6 DRG. Although the majority of FG-labeled perikarya contained neither CGRP nor NADPH-diaphorase, small subpopulations of perikarya contained either CGRP immunoreactivity, NADPH-diaphorase, or both. A unilateral pudendal nerve transection virtually eliminated (> 99%) FG labeling in the ipsilateral L6 DRG. These data suggest that NADPH-diaphorase and CGRP are present, either together or separately, within a subpopulation of penile afferent perikarya. In addition, CGRP-immunoreactive afferent nerve fibers reach the penis primarily via the pudendal nerves. Finally, NADPH-diaphorase-positive penile afferents may be another important source of nitric oxide (NO) for penile tumescence.


Permeability of the blood-brain barrier to peptides: an approach to the development of therapeutically useful analogs.

Peptides have been shown in both in vivo and in vitro systems to cross the blood-brain barrier (BBB) and so affect function on the side contralateral to their origin. Some peptides cross primarily by transmembrane diffusion, a nonsaturable mechanism largely dependent on the lipid solubility of the peptide. Other peptides are transported by saturable systems across the BBB. These transport systems can be in the CNS to blood direction, as in the cases of Tyr-MIF-1 and methionine enkephalin, in the blood to CNS direction, as in the case of peptide T, or bidirectional, as in the case of LHRH. Other factors that also affect the amount of peptide crossing the BBB include binding in blood, volume of distribution, enzymatic resistance, and half-time disappearance from the blood. An in vitro model of the BBB has been characterized and used to confirm that peptides can cross the BBB. Results with the model agree with those obtained in vivo and have been used to study the permeability of the BBB to peptides, the effect of peptides on BBB integrity, the cellular pathway peptides and proteins use to cross the BBB, and the ability of the BBB to degrade peptides. The in vivo and in vitro methods have been used together to develop halogenated enkephalin analogs that are enzymatically resistant, cross the BBB readily to accumulate in areas of the brain rich in opiate receptors, and are powerful analgesics.(ABSTRACT TRUNCATED AT 250 WORDS)


The differing predictive values of oestrogen receptor assays for large breast cancers.

Thirty elderly patients with T3 or T4 breast cancer underwent a wedge biopsy for radioligand-binding assay (RLA) of oestrogen receptor (ER) activity. A second, separate group of 21 elderly patients with T3 and T4 breast cancers underwent fine needle aspiration biopsy (FNA) for immunocytochemical assay of ER (ER-ICA). All the women received tamoxifen as primary treatment and response was assessed by UICC criteria. Tumour ER concentration by RLA was correlated with both response (Spearman's R = + 0.52) and time to progression (R = + 0.76). Nine patients with receptor-rich tumours (> 100 fmol/mg protein) failed to show a response. However, the percentage of cells staining for ER by ER-ICA assay was much more strongly related to the likelihood of response (R = + 0.89); no patient with < 20% cells staining responded. Wedge biopsy and the biochemical determination of ER activity is of limited value in predicting the likely response to tamoxifen; ER-ICA assays on such tumours may be more informative.


What are the benefits of routine breast cancer follow-up?

The value of follow-up after potentially curative treatment of breast cancer remains controversial. Recurrence-free women (n = 402) attending a breast clinic over a 3 month period were studied. The women attended 423 appointments, 412 of which were routine. Eleven were requested by the patient or general practitioner (interval appointments). All 11 interval and 19 of the routine appointments resulted in investigations for possible recurrence. Three (27%) interval appointments and four (1%) routine appointments resulted in the diagnosis of a recurrence (P < 10(-5). The attitudes of 285 patients to follow-up were investigated by questionnaire. Two hundred and twenty-three (78%) questionnaires were completed. Regular follow-up in the breast clinic was preferred to attendance only when symptomatic by 190 (85%) women and 169 (76%) preferred regular breast clinic visits to general practitioner follow-up. Most women (n = 174) (81%) said they felt reassured and less anxious having attended the breast clinic. Routine follow-up after potentially curative treatment of breast cancer is inefficient in the detection of recurrence. It is, however, highly rated for providing reassurance and reducing anxiety. Reassurance rather than detection of recurrence may be the most important function of the breast cancer follow-up clinic.


Endogenous sex hormones and bone mineral density among community-based postmenopausal women.

In order to describe the relationships between endogenous sex hormones and bone mineral density in healthy postmenopausal women, we carried out a cross-sectional study of 90 community-based women, all at least one year since their last menstrual period (mean 9.6 +/- 4.9 years, range 1-22) and with a serum oestradiol level less than 100 pmol/l. None was currently using hormone replacement therapy. Serum oestradiol, testosterone, sex hormone binding globulin, dehydroepiandrosterone sulphate, and androstenedione were measured using standard techniques. Free oestradiol and testosterone indices were derived as the ratio of total hormone to sex hormone binding globulin, respectively. Total body, spine and hip bone mineral density (g/cm2) were measured by dual energy X-ray absorptiometry. Significant positive correlations were found between the free oestradiol and testosterone indices and bone mineral density at all sites. These relationships remained significant for the free oestradiol index after adjustment for age and body mass index. By stepwise multiple regression analysis, the free oestradiol index was an independent predictor of total body, spine and hip bone mineral density, accounting for 4-17% of the variance. These findings suggest an independent positive relationship between endogenous free oestradiol and total body, spine and hip bone mass even in the late postmenopause.


Crohn's disease in Bangladeshis and Europeans in Britain: an epidemiological comparison in Tower Hamlets.

The incidence of Crohn's disease in a defined Bangladeshi community was assessed in a retrospective, epidemiological study in the London Borough of Tower Hamlets from 1972 to 1989. The borough population of 164,000 includes over 28,000 Bangladeshis. Potential cases were identified from hospital pathology and medical records. There were 99 cases of Crohn's disease during the study period, of which five were Bangladeshi. The mean standardized incidence in Bangladeshis was 1.2/10(5)/year in the 1970s and 2.3/10(5)/year in the 1980s compared with 3.8/10(5)/year and 4.1/10(5)/year in Europeans, and 4.6/10(5)/year and 5.4/10(5)/year in West Indians, respectively. None of the changes with time was statistically significant. There were no cases amongst Hindus. The relative risk to Europeans, compared to Bangladeshis, was 2.5 during the 1970s and 2.0 in the 1980s. The difference between European incidence and that of other ethnic groups was not statistically significant; however, the number of Bangladeshi cases was small (five), and diminishes the power of the study. The apparent similarity of the incidences of Crohn's disease in Bangladeshis and Europeans contrasts with findings in other South Asians. Further investigations of the differences in incidence of Crohn's disease in South Asians is needed.


Family therapy.

The discipline of family therapy, one of the psychotherapies, is defined and illustrated clinically in this article using case material. References are provided which allow further reading about family systems medicine.


Further evidence for differential regulation of follicle-stimulating hormone (FSH) and luteinizing hormone (LH): increased FSH and decreased LH levels in a patient with familial pure gonadal dysgenesis.

There is experimental evidence that a portion of follicle-stimulating hormone (FSH) secretion is independent of hypothalamic influences. A 29 year old woman with familial pure gonadal dysgenesis developed myelodysplastic syndrome. Endocrine investigations showed discrepancy between serum FSH and luteinizing hormone (LH) levels. FSH levels remained elevated while LH levels decreased. The FSH to LH ratio was 10 (normal 2-2.5). The fall in LH is likely to be due to factor(s) involved directly and specifically in LH synthesis and release. Exogenous LH releasing hormone administration as well as hormonal replacement treatment increased LH levels. The FSH to LH ratio decreased to 7. This case supports the hypothesis of differential regulation of FSH and LH, and that FSH secretion is at least partly autonomous.


Splenic rupture following splenic vein thrombosis in a man with protein S deficiency.

We present a case of spontaneous splenic rupture in a man with splenic vein thrombosis. The splenic vein thrombosis appears to have been caused by protein S deficiency. We are not aware of this having been described before.


Streptococcus bovis endocarditis as a presenting manifestation of idiopathic ulcerative colitis.

Streptococcus bovis bacteraemia and endocarditis have been associated with several gastrointestinal diseases, mainly malignant or potentially malignant tumours, and less commonly non-malignant gastrointestinal disorders. We describe a 73 year old man in whom Streptococcus bovis endocarditis developed, and was the presenting manifestation of undiagnosed quiescent ulcerative colitis. Such an association has not been described previously.


Carnitine deficiency associated with long-term pivampicillin treatment: the effect of a replacement therapy regime.

A 51 year old female developed a skeletal muscle myopathy after 3 months of pivampicillin therapy. Pivampicillin can cause carnitine deficiency due to the pivalic acid side group. Plasma carnitine content and the patients symptoms failed to improve significantly on discontinuing the drug. Oral carnitine replacement therapy was administered for 6 weeks but the patient's plasma carnitine levels responded only slowly to this treatment. It is suggested that pivampicillin inhibits uptake of carnitine from the gut and may either directly or indirectly depress endogenous carnitine synthesis. In such cases a more aggressive carnitine replacement regime is indicated and pivampicillin should be avoided in patients requiring long-term antibiotic administration.


Prediction of mortality in patients in acute medical wards using basic laboratory and anthropometric data.

The value of anthropometric and biochemical indices in predicting short-term mortality among patients in general medical wards was assessed in 294 patients admitted consecutively to a district hospital over a one month period. Using a stepwise logistic regression model and supported by the linear discriminant analysis method, mortality within 3 months could be predicted with sensitivity of 83% and specificity of 84% using the following variables: sex, functional ability, urea, total protein, alkaline phosphatase and albumin-adjusted calcium. Addition of anthropometric values and biochemical nutritional indices did little to improve the accuracy of the prediction, contrary to previous findings among surgical patients and elderly residents of long-term care institutions.


Complications associated with percutaneous needle biopsy of the liver when one, two or three specimens are taken.

The diagnostic yield of blind percutaneous liver biopsy is improved when two or three specimens are taken during the procedure by redirecting the needle through a single entry-site, without exposing the patient to a greater risk of complications provided that standard precautions are taken. This study was designed to obtain further data on the safety of this procedure at King Edward VIII Hospital, Durban. During the period 1984-1990 (inclusive) a total of 2,646 biopsies were carried out: a single specimen was obtained in 834 patients, two specimens in 983 patients and three in 829 patients. Complications directly attributable to the procedure occurred in 24 patients who had one specimen, 20 who had two, and 19 who had three specimens taken during the biopsy. A single specimen had been obtained from three of the eight patients who had died, two specimens had been taken from another patient, and three specimens were obtained from the other four patients, i.e. patients in whom two or three specimens were taken did not have a higher incidence of pain, symptomatic hypotension, biliary peritonitis or death than those in whom one specimen was taken. Accordingly, when blind percutaneous needle biopsy of the liver is carried out, two specimens should be obtained by redirecting the needle through a single entry site as this improves the diagnostic yield without increasing complications. The morbidity and mortality associated with liver biopsy in this hospital is, however, high. Good technique, careful monitoring of patients after biopsy and prompt and aggressive resuscitation are essential if the mortality rate is to be reduced.


Late onset epilepsy in undiagnosed tuberous sclerosis.

A 67 year old woman first developed left-sided sensorimotor seizures postoperatively in association with infection and mild hyponatraemia. She was found to have previously unrecognized tuberous sclerosis, with gross pathognomic features: periungual fibromata, facial angiofibromata, calcified subependymal nodules, cortical tubers and multiple renal angiomyolipomata. Her son who was epileptic was also found to have other mild features of tuberous sclerosis as a result. As far as we are aware our patient is the oldest for the first presentation of tuberous sclerosis.


Amoebic psoas and liver abscesses.

A 28 year old woman with a history of a dysenteric illness and documented Campylobacter infection presented with amoebic psoas and liver abscesses. A review of the literature of the last 20 years did not yield any reports of an amoebic psoas abscess.


Strongyloides stercoralis hyperinfection in a patient with angioimmunoblastic lymphadenopathy.

A 29 year old Bengali male patient on chemotherapy for angioimmunoblastic lymphadenopathy developed Strongyloides hyperinfection syndrome 3 months after being treated with a single 3 day course of thiabendazole. His complicated hospitalization and successful management are described. Prevention of this potentially fatal disease in immunocompromised patients by early diagnosis and proper management of intestinal strongyloidiasis is emphasized.


Familial Conn's syndrome.

We describe the occurrence of primary hyperaldosteronism in two sisters. Although this is only the second published report of familial Conn's syndrome, it does have implications for the relatives of patients with Conn's syndrome and these are discussed.


A cis-acting element involved in mouse tyrosinase gene expression and partial purification of its binding protein.

The tyrosinase gene is specifically expressed in melanocytes. Understanding the molecular basis of tissue-specific expression of the tyrosinase gene will greatly explain the mechanisms controlling pigmentation. We report a nucleotide sequence, TGATGTATTC, located -236 base pairs upstream of the transcription start site, that enhances tyrosinase gene expression in mouse melanoma cells. The sequence is referred to as the tyrosinase element-1 (TE-1). TE-1 was protected from DNase I cleavage by pigment cell nuclear extracts but was not protected by non-pigment cell nuclear extract. Partial purification of TE-1 binding protein (TEBP-1) was performed from the B16 mouse melanoma cell nuclear extract using biotin-cellulose affinity chromatography. The affinity-purified fraction exhibited binding to the DNA fragment containing TE-1, and to a synthetic oligomer representing TE-1. UV-cross-linking indicated that the size of TEBP-1 is approximately 49 kD. TE-1 also directed enhanced CAT activity in the B16 melanoma cells but not in non-pigment cells. These data indicate that TE-1 may be an enhancer element that is responsible for pigment cell specific expression of the tyrosinase gene.


Isolation and characterization of a chicken tyrosinase cDNA.

Complementary DNA clones coding for chicken tyrosinase were isolated from retinal pigmented epithelium of chicken embryo. Sequence analysis shows that one of the cDNA clones consisting of 1,997 nucleotides has an open reading frame coding for 529 amino acids. The deduced protein has nine N-glycosylation sites and a transmembrane region. A sequence comparison of the deduced chicken tyrosinase with the mouse and human homologues revealed that amino acid sequences are conserved for the entire polypeptides. Seventy-two percent and 73% of amino acids in the chicken sequence are identical to that of the mouse and human tyrosinases, respectively. Histidines neighboring the postulated copper-binding sites and the cysteines are well conserved. RNA blotting analysis showed that a major transcript of 2.5 kb is detected in retinal pigmented epithelium of a 9-day-old chicken embryo.


Cystic hygroma and congenital diaphragmatic hernia: early prenatal sonographic evaluation of Fryns' syndrome.

We report a case of cystic hygroma and diffuse lymphangiectasia detected by sonogram at 12 weeks' gestation. Fetal karyotype was normal. At 20 weeks' gestation, herniation of the bowel into the chest was noted. At delivery, the infant was diagnosed as having Fryns' syndrome. This is the first reported case of Fryns' syndrome presenting with cystic hygroma.


Prenatal diagnosis of Chediak-Higashi syndrome.

We report the first prenatal diagnosis of an affected fetus with Chediak-Higashi syndrome (CHS). Diagnosis was accomplished via fetal blood sampling at 17 menstrual weeks and was confirmed after birth. Retrospective measurement of the largest acid phosphatase-positive lysosomes in cultured amniotic fluid cells and chorionic villus cells showed that in CHS these lysosomes are significantly larger than those in normal cells. This method may be used for prenatal diagnosis of CHS by amniocentesis and chorionic villus sampling (CVS).


Screening for fetal Down syndrome with maternal serum hCG and oestriol: a prospective study.

We report the preliminary results of a prospective study aimed at evaluating the effectiveness of Down syndrome (DS) screening using second-trimester measurement of maternal serum human chorionic gonadotrophin (hCG) and unconjugated oestriol (uE3) together with maternal age. Reference values for hCG, uE3, and the hCG/uE3 ratio in normal pregnancies were established from more than 3000 normal gestations and found to follow a log-normal statistical distribution. Risk evaluation was made using reference values for affected pregnancies from retrospective studies. Screening of 10,000 women under 38 years resulted in 412 amniocenteses and the prenatal diagnosis of six cases of DS, whereas four cases remained undetected until term. In a parallel study, diagnostic amniocentesis was performed in women over 38 years and in women with a previous affected child, and an evaluation of the risk of fetal DS based on serum hCG and uE3 levels was made in all cases. Fourteen cases of DS were detected. Median values for hCG and uE3 in the 24 affected pregnancies were close to the 90th and tenth centiles of the normal reference values, respectively, and thus are in good agreement with the values reported by others in retrospective studies.


Rare non-mosaic trisomies in chorionic villus tissue not confirmed at amniocentesis.

This paper reports eight cases of non-mosaic, rare, and typically lethal trisomies diagnosed in chorionic villi and not confirmed by amniocentesis. Four cases were 47,XX,+16; two cases were 47,XX,+2; one was 47,XX,+12; and one was 47,XY,+7. There have been no known complications in any of these gestations. These eight cases were found in a series of approximately 12,000 samples processed in our laboratory (0.07 per cent). We conclude that (1) rare non-mosaic trisomy not reflecting the fetal condition is an occasional source of diagnostic ambiguity in chorionic villus sampling; and (2) when encountered, a follow-up amniocentesis should be recommended to the patient to confirm or rule out the abnormality. We propose the term 'confined placental abnormality' to describe non-mosaic trisomies and other related abnormalities found only in chorionic tissue.


A simple electrophoretic procedure for fetal diagnosis of beta-thalassaemia due to short deletions.

This study describes three couples at risk for homozygous beta-thalassaemia in which one of the partners carried a short deletion beta-thalassaemia defect. Detection of short deletions in trophoblast DNA was accomplished by the very simple procedure of non-denaturing polyacrylamide gel electrophoresis. This method may be applied to detect beta-thalassaemia mutations due to deletion or addition of more than two nucleotides.


Prenatal identification of a 45,X/46,Xder(Y) mosaicism and confirmation by high resolution cytogenetics and fluorescence in situ hybridization.

A 45,X/46,Xder(Y) mosaicism detected prenatally was shown to have a rare Y inversion-duplication or Y/Y translocation which can only be identified by a combination of high resolution cytogenetics and fluorescence in situ hybridization. The present data indicate the usefulness and importance of chromosome-specific probes in the identification and characterization of chromosome rearrangements.


Prenatal diagnosis of giant cystic hygroma: prognosis, counselling, and management; case presentation and review of the recent literature.

Cystic hygromas have historically been associated with a grim prognosis when discovered during prenatal sonographic study of the fetus. This same grim prognosis is not observed by the paediatric surgeon who evaluates the neonate or paediatric patient. We present a fetal patient with a massive anterior cystic hygroma discovered in the third trimester prior to 30 weeks. This case and a review of the literature suggest tailoring the prognosis by category when counselling patients: (1) first trimester, normal karyotype--good; (2) first trimester, abnormal karyotype--poor; (3) second trimester and early third--poor to guarded; and (4) mid to late third trimester--good.


Analysis of chromosome 21 copy number in uncultured amniocytes by fluorescence in situ hybridization using a cosmid contig.

A comparison of the use of chromosome 21-specific libraries, DOP-PCR 21 paints, yeast artificial chromosome (YAC) clones, single cosmids, and a 21q cosmid contig as probes for the detection of the copy number of chromosome 21 in interphase cells by fluorescence in situ hybridization shows that the cosmid contig is a satisfactory probe for interphase analysis of chromosome 21. The contig cCMP21.a, which is 55 kb in length, is highly chromosome 21-specific and produces intense, compact signals in a high proportion of interphase cells. A retrospective blind analysis of coded uncultured amniotic fluid samples correctly detected four trisomy 21 cases out of 49 samples.


Prenatal diagnosis of monosomy 18 and ring chromosome 18 mosaicism.

The case of monosomy 18/ring chromosome 18 mosaicism which was detected prenatally by amniocentesis is presented. The pregnancy was terminated in week 18. Autopsy showed complex malformation of the fetus consisting of cebocephaly, hypotelorism, microphthalmia, severe defects of brain development, and arrest of placental maturation.


Normal karyotype in cultured chorionic villus cells, but mosaicism in amniotic and fetal cells.

A case with a normal male karyotype in cultured chorionic villus cells, but 46,XY/45,X/46,X,i(Yq) mosaicism in amniotic and fetal tissue is reported. The fetus was a phenotypic male. Pathological examination revealed discrete features, which might indicate a syndrome, and histological examination showed large, bright cells in the tubules of the testes. Possible explanations for discordance between the karyotype of embryonic and extraembryonic tissue are discussed.


Neonatal alloimmune thrombocytopenia due to anti-P1A1 (anti-HPA-1a): importance of paternal and fetal platelet typing for assessment of fetal risk.

Neonatal alloimmune thrombocytopenia (NAIT), which usually involves sensitization to P1A1 (HPA-1a), may have devastating complications for the fetus. These may be prevented by antenatal treatment of severe cases with either maternally administered high-dose gamma-globulin and/or repeated intrauterine platelet transfusions. Determination of the paternal platelet phenotype is useful for counseling parents who have had one or more affected pregnancies. This report of an unaffected pregnancy in a woman with a history of previous pregnancies complicated by NAIT illustrates the role of paternal and fetal platelet phenotyping in managing existing pregnancies at risk of NAIT.


Chromosomal abnormalities associated with a single umbilical artery.

A single umbilical artery was seen in 10 out of 117 cytogenetically abnormal pregnancies. The abnormal karyotypes found to be associated with a single umbilical artery were trisomy 18 (n = 5), monosomy X (n = 2), triploidy (n = 1), sex chromosome (47,XYY; n = 1) and translocation (46t(X,5)(q13p15);n = 1). With the exception of the translocation case, all cases with a single umbilical artery had anatomical defects which were detectable ultrasonographically. This suggests that a single umbilical artery alone is not an indication for prenatal fetal karyotyping.


[Isolation of Toxoplasma gondii by cellular culture in HIV infected patients].

Nine hundred and eight biological samples obtained from HIV-infected patients were examined for Toxoplasma gondii by a tissue culture method. Sixty-two isolations of Toxoplasma gondii were made in 43 patients. Fourteen isolations were made from tissue biopsies (brain 4, striated muscle 2, liver 1), bone marrow aspirates (4 cases), pericardial or pleural effusions (3 cases) and vitreous body (1). In 6 cases, a parasitic dissemination was evidenced by the demonstration of Toxoplasma in blood or other tissues or body fluids. Toxoplasma organisms were demonstrated in the bronchoalveolar lavage fluid of 19 patients; this was associated with a parasitaemia in 6 of the 10 patients whose blood sample was cultured at the same time. Among 273 blood samples cultured, 29 were positive for Toxoplasma (24 patients); all patients with parasitaemia had clinical symptoms, but only 8 of them had clinical or radiological symptoms suggestive of a cerebral localization; this suggests that the presence of a parasitaemia is fairly indicative of an extra cerebral localization of toxoplasmosis. In 11 patients, blood was examined after treatment was initiated; in 8 patients parasitaemia was undetectable at the first examination after treatment (1 to 15 days after initiation of therapy), whereas in 3 patients sampled 1, 4 or 6 days respectively after treatment a persistent parasitaemia could be demonstrated. These results clearly show that the tissue culture method is efficient and sensitive to provide an early evidence of infection (4 days), and may prove useful to evaluate therapeutic effectiveness.


[Diagnosis of lymphatic metastases in pelvic urologic tumors. Value of puncture biopsy].

In 119 patients with pelvic urogenital tumours the diagnosis of lymph node metastasis was made by lymphography-guided fine needle biopsy. The results of this technique, performed without anaesthesia and devoid of morbidity, could be interpreted in 88 percent of the cases. In the search for micro- and macroscopically invaded lymph nodes fine needle biopsy had a sensitivity of 66 percent, a specificity of 100 percent, a positive predictive value of 100 percent and a negative predictive value of 92.3 percent. In cases with macroscopically invaded nodes its sensitivity was 82.3 percent.


[Appendectomy, a risk factor for ectopic pregnancy].

As part of a case-control study of ectopic pregnancy, we evaluated the potential etiological role of appendectomy. Previous appendectomy was associated with an increased risk of ectopic pregnancy (adjusted Odds-ratio: 2.2; 95 percent CI: 1.5-3.2). Ruptured appendix did not appear to be more strongly associated with an increased risk of ectopic pregnancy than unruptured appendix. Such confounding factors as absence of pathological diagnosis of appendicitis and relationship between age of appendectomy and age of first sexual intercourse are discussed. This study provides an additional argument in favor of laparoscopy in childbearing age to diagnose appendicitis and salpingitis.


[Hermaphroditism and male pseudohermaphroditism].

In the human embryo, sex is all in the genes. Later on, the male and female sexual characters, which are products of the expression of all individual genomes, differentiate men from women. In this paper, the embryogenesis and morphology of true hermaphroditism and male pseudo-hermaphroditism are studied. These are intersexual states determined by errors in genital programme transmission. A relationship is established between the biochemical identification of substances secreted by the testis and the evolution of sexual characters. The genesis of sexual abnormalities according to the stage when the testicular deficit appears is envisaged. The clinical, anatomical, histological and biochemical aspects of these intersexual states are described.


[Enzymatic reactions in biotechnology (48th Bach lecture)].

The paper is the 48th Bach Lecture presented under the same title. It covers the biochemical mechanisms of the biogenesis of microbial biosynthetic products, role of acetyl-CoA, function of the succinate-glycine cycle, reactions of the hexose-monophosphate pathway of carbon metabolism. The reversible action of hydrolases in enzymatic catalysis and degradation of xenobiotics are discussed. The data on redox reactions are pooled. Such modern biotechnological processes as epoxidation, synthesis of acrylamide and some monomers involved in chemical syntheses of polymers, synthesis of oligosaccharide and fluorine-containing amino acids are considered. Promising commercial applications of biocatalysis are discussed.


[Methods of detecting and determining nitrogen-containing mycotoxins].

The influence of various nitrogen functional groups used for extraction cleanup and determination of N-containing mycotoxins (NM) in feeds and foodstuffs have been considered. TLC and LC are the most common techniques for detection and determination of nitrogen-containing mycotoxins. Gas chromatography has been used for determination (with or without derivatization) of several nitrogen-containing mycotoxins and/or their degradation products. Immunochemical techniques, in particular ELISA are available for only a very limited number of NM (e.g. ochratoxin A). Numerous methods for determination of ochratoxin A in feeds, grains, animal products and other foodstuffs have been developed. Methods for which recoveries have been carried out on spiked samples are also available for several other NM.


[Various aspects of regulating the synthesis of ergot alkaloids].

The regulation of ergot alkaloid (EA) biosynthesis both at the genetic level and at the level of physiological realization is discussed. The genes involved in EA synthesis are shown to be under rigorous metabolic control. Circumstantial evidence links the initiation of the EA metabolism to changes in some parameters viz morphological feature, concentrations of enzymes and their substrates, contents of nutrients, and external stress.


[Penicillium-species fungi--producers of ochratoxin A in grain].

The occurrence of ochratoxin A and ochratoxigenic fungi in the commercial batches of various domestic grains (wheat, rye, barley, corn and rice) has been studied. Penicillium cyclopium, P. viridicatum and P. chrysogenum isolated from grain synthesized on a sucrose-yeast medium predominantly patulin, penicillic and kojic acids. Only 4.4% of the fungal isolates were able to synthesize ochratoxin A. The concentration of the mycotoxin accumulated by the fungi was less than 500 micrograms/kg. 230 samples of wheat and 502 samples of corn were examined. The analysis showed that ochratoxin A was present in 0.9% and 0.1% of samples tested, respectively. The mycotoxin accumulated in grain mainly during its spontaneous heating and was concentrated in mold-damaged kernels.


[Pleural diseases in magnetic resonance tomography (MRT)].

MR images of 48 patients with histologically confirmed benign and malignant diseases of the pleura were retrospectively compared with CT and bioptically/surgically obtained findings. In 47/48 patients pathological changes of the pleura were visualized by increased signal intensities on T2-weighted and contrast enhanced T1-weighted MR images. This lead to a slightly improved sensitivity compared to CT, where pathological pleura findings were confirmed in 45/48 patients. MRI was able to identify 24/28 confirmed pleural effusions, whereas CT was successful in 26/28 patients. In two cases effusions not identified on CT were visible on T2-weighted MRI. 4 pleural effusions were missed with MRI.. On CT images differentiation of pleural changes vs effusions or adjacent lesions of lung parenchyma was successful in 20/28 and in 17/23 cases, respectively. Contrast enhanced T1-weighted images achieved the highest diagnostic accuracy with 22/28 and 20/23 cases, respectively. Signal intensities on MRI were unsuitable as sole criterion for the differentiation of benign and malignant diseases of the pleura. Contour and pattern of spreading of pleural changes were helpful in differential diagnosis. Nodular changes, thickening of more than 10 mm and mediastinal, circumferential and entire hemithoracic affection of the pleura were suggestive for malignant pleural disease. Infiltration of the diaphragm and the chest wall were most indicative for malignancy; here MRI (2/2 resp. 18/19 cases) was superior to CT (0/2 resp. 14/19 cases). CT was superior in the detection of pleural calcifications and osseous destruction.(ABSTRACT TRUNCATED AT 250 WORDS)


[Biosynthesis of ergot alkaloids. Some new results on an old problem (Review)].

The biosynthetic pathway leading from L-tryptophan, mevalonic acid and methionine to the tetracyclic ergoline ring system of the ergot alkaloids in Claviceps species is reviewed. This pathway entails many mechanistically intriguing features. Recent studies are also discussed which reveal the stereochemical course of the isoprenylation of tryptophan and of the N-methylation of dimethylallyltryptophan (DMAT) and which shed some light on the likely steps leading from the open-chain precursors, N-methyl-DMAT to the tricyclic intermediate, chanoclavine-1. Finally, some plans are outlined to probe the evolutionary relationship of ergot alkaloid biosynthesis in fungi to that in higher plants of the family Convolvulaceae.


[Expression of TNF-alpha in alveolar macrophages after stimulation with quartz dust, welding fume dust and asbestos fibers].

Alveolar macrophages have a potential for expressing and excreting many factors that are immunologically active and active on cytokines (monokines and lymphokines) and are thus indirectly involved in the genesis of pulmonary fibroses. One of these factors is the tumour necrosis factor alpha (TNF alpha). In the study presented here, the expression of TNF alpha-mRNA was investigated in macrophages stimulated in vitro with quartz dust, dust from cinders of welding furnaces, and asbestos, using non-radioactive in situ hybridization. There was a marked dependence of the expression of this cytokine on both time and stimulation. Macrophages stimulated by quartz dust showed the highest rate of expression compared with controls and other related stimuli. In addition, all stimuli yielded an expression that was elevated for a short period only and reached its peak after four hours. The results permit the conclusion that various professionally inhaled dusts possess different risk potentials in respect of lung damage mediated by macrophages and do not behave uniformly.


[The value of physical therapy with VRP 1-Desitin ("Flutter")].

Preliminary examinations with an innovative device for physiotherapy, VRP 1-Desitin ("Flutter"), in patients suffering from chronic mucus retention and bronchial collapse gave encouraging results. Therefore, we tried to confirm these findings and to evaluate the use of this new physiotherapy. It is based on oscillations of air in the respiratory tract during expiration (rate about 2 to 32 Hertz) diminishing adhesiveness of bronchial mucus and bronchial collapse. Pressure and flow changing depend on the position of mouth-piece and effort of breathing. In order to establish the efficiency of the VRP 1 a comparing investigation was initiated. 20 patients with cystic fibrosis, aged 7 to 28 years, performed physiotherapy with VRP 1 and autogenic drainage (AD), respectively, in a randomized order one after another, each physiotherapy taking twenty minutes. The expectorated sputum was weighed by means of a precision balance. Mean values during VRP 1 treatment were 5.0 g (range 0 to 12.0 g), during AD 4.8 g (range 0 to 11.7 g). There was no statistical difference (p < 0.05). The results were not influenced by the order of physiotherapy. VRP 1 physiotherapy is as effective as AD with respect to sputum elimination. In opposite to other methods not requiring a helping person it is simple to teach and to learn. It may be performed by young children (> or = 3 years) and adults, also in combination with inhalation. Thus, VRP 1 appears to be a real enrichment in physiotherapy.


[Spontaneous lung torsion after acute pleuropneumonia].

We report on a case of spontaneous torsion of the right lung in a 59 years old woman which occurred after an acute pneumonia followed by chronic empyema and progressive dyspnea with marked respiratory disability. Despite extensive diagnostic procedures including bronchoscopy and bronchography the true diagnosis could be established only by thoracotomy performed in order to cure the chronic empyema. The abnormal hilar rigidity by preexisting calcified sarcoidosis of the lymph-nodes is suggested to be a major risk factor for developing lung torsion as it has been emphasized in a few similar reports from the literature. Surgical reposition of the displaced lung is the most effective treatment and can save and restitute lung structure and function even in patients with prolonged course and delayed diagnosis.


[Hepatotoxicity of cyclochlorotine--a cyclic peptide produced by Penicillium islandicum].

Toxicological investigations of "Yellow Rice" which have been contaminated with various Penicillium species have shown that Penicillium islandicum apart from well-known hepatotoxic mycotoxin, lyteoskyrin synthesizes cyclochlorotine (chloropeptide, CP), which is also hepatotoxic. Isolation of chloropeptide and its chemical characteristics, acute toxicity and biochemical alterations, tissue distribution and excretion, deformation of hepatic cells, and interaction with cytoskeleton filaments are described. It is shown that the hepatotoxicity of CP is inactivated by dehalogenation of CP by the cytochrome P-450 system.


[Primary pulmonary nodular amyloidosis and multiple emphysematous bullae in Sjögren syndrome].

The authors report on a very rare case of an isolated primary nodular pulmonary amyloidosis with multiple emphysematous bullae in Sjögren's syndrome. The circular foci present in both lungs in disseminated form were immunohistochemically speaking amyloid deposits of the AL-lambda type. There were no pointers to other organ manifestations or monoclonal immunoglobulins in the serum and/or urine.


[Fumonisins--new metabolites of Fusarium moniliforme--as contaminants of corn].

Strains of the Fusarium moniliforme fungi, widely distributed contaminants of maize are shown to be highly toxic and carcinogenic and cause various animal and human diseases. The effect of temperature and incubation period on the production of fumonisins by F. moniliforme have been studied. The overall maximum yield of fumonisins was 17.5 g/kg maize. A high-performance liquid chromatographic method for the quantitative determination of fumonisins is proposed. The structural analysis of their tetramethylethers was performed by the mass-spectrometry method. It has been established that fumonisins are causative factors in the toxicity of horse leukoencephalomalacia. The possible role of fumonisins in the etiology of oesophageal cancer is discussed.


[A bioluminescence method of determining the activity of NAD-dependent hydrogenase].

An analytical multienzyme system composed of NAD-dependent hydrogenase of Alcaligenes eutrophus, and reductase and luciferase from luminous bacteria was studied. The rate of luminescence increase of this system was found to be proportional to hydrogenase activity. The apparent Michaelis constants for NAD and hydrogen were determined (5 and 40 microM, respectively). The pH optimum is 7.5-9.0. Over the NAD concentration range from 20 to 100 microM, the rate of luminescence increase changed by less than 10%. At higher concentrations of NAD a monotonous decreasing of the rate of luminescence increase was observed. The proposed multienzyme system can be used for measuring the hydrogenase activity and hydrogen concentration. The high sensitivity to hydrogen (0.1 nmol in sample) and to hydrogenase (0.5 mU) and specificity of the system enable its application in the development of a biosensor for rapid detection of hydrogen in a medium.


Antidepressants--do they decrease or increase suicidality?

Based on an intensive review of the literature, the question was analyzed as to whether antidepressants have an influence on suicidality and whether there are specific differences between certain subgroups of antidepressants. In general, antidepressants reduce suicidal ideations in depressive patients. A faster onset of this kind of action in serotonin-reuptake inhibitors is not yet completely proved. The hypothesis, described by clinicians, of a specific suicidality-increasing risk being associated with a certain group of antidepressants (e.g., antidepressants with a drive-enhancing, non-sedating clinical profile, drugs with a certain biochemical mode of action) has hitherto not been confirmed in control-group studies. An unspecific induction of suicidality, observable also under other psychoactive drugs, appears to be quite rare and occurs only under predisposing conditions, such as personality disorders and comedication with other drugs.


Brofaromine in panic disorder: a pilot study with a new reversible inhibitor of monoamine oxidase-A.

The therapeutic efficacy of brofaromine--a new reversible and short acting MAO-A inhibitor--was evaluated in 14 inpatients with a panic disorder. In an open trial, the patients were treated with placebo during the first week and with 150 mg brofaromine per day during the following four weeks. In all patients a distinct improvement in both anxiety and depressive symptoms was observed under the active drug. Treatment outcome was the same in patients with and without a concomitant major depressive episode. No side-effects of any note were reported. Our findings suggest that the MAO-A inhibitor brofaromine is an effective drug in the treatment of anxiety disorders.


Haloperidol and lorazepam combined: clinical effects and drug plasma levels in the treatment of acute schizophrenic psychosis.

In 61 acute schizophrenic patients the effects of haloperidol (HPL) and lorazepam combined vs. HPL alone and the interaction between these drugs were evaluated. Patients were assigned to groups randomly. The study design was open. Study duration was 28 days. Psychopathology was evaluated on the basis of BPRS scores. Extrapyramidal side-effects were rated according to Simpson and Angus (1970). Pharmacological parameters included serum levels of lorazepam, HPL, and reduced HPL. Mean daily lorazepam dosage was 0.05 mg/kg, mean HPL dosage 0.5 mg/kg. None of the patients treated with lorazepam and HPL achieved better BPRS total or subscores, nor did their condition improve faster than in patients treated with HPL alone. A significant linear relationship between lorazepam serum levels and oral dosage was found, but none between lorazepam serum levels and BPRS total score, subscore reduction, or extrapyramidal side-effects. The authors conclude that beneficial effects of lorazepam in the treatment of acute psychosis are scant and may not justify the risks incurred with routine comedication of lorazepam.


Electroconvulsive therapy in a geriatric patient with multiple bone fractures and generalized plasmocytoma.

Electroconvulsive therapy (ECT) is a highly effective treatment for patients with severe major depressive disorder. ECT can safely be administered even to medically ill, high-risk patients; we report on the complete remission of depressive psychopathology following five unilateral ECT treatments in a suicidal geriatric patient with concurrent prior venous thrombosis, coronary heart disease, multiple myeloma, glaucoma, bilateral petrous bone fractures, and a femoral neck fracture. Most medical complications during ECT can be managed with interdisciplinary cooperation.


[Character formation and interactions].

This paper details the impact of constitution endowment, e.g. temperament and interaction with the parents, e.g. transaction on character development. Adult and child analytic material are used to illustrate this process.


[A psychoanalytic model at the "Menninger Clinic"].

This paper describes the psychiatric treatment of adolescents on one of the long term inpatient units of the Children's Hospital at Menninger in Topeka, Kansas. The conceptual framework for this treatment is psychoanalytic. Dr. Stamm's paper describes how hospital's "holding environment" (Winnicott, 1965) and the individual and family therapy converge to facilitate emotional growth and change. Central to psychoanalytic hospital treatment is an understanding of transference/countertransference with each adolescent.


[Tourette's syndrome: psychopathology of development in a model of neuropsychiatric dysfunction in children].

The complex neuropsychiatric disorder described by Gilles de la Tourette is a childhood onset, generally lifelong condition diagnosed on the basis of multiple, everchanging motor and vocal tics. Genetic evidence indicates that the vulnerability to Tourette's Syndrome (TS) is transmitted as an autosomal dominant genetic trait. This vulnerability has a broad range of expression, from full-blown TS to chronic multiple tics; an alternate manifestation may be obsessive compulsive disorder. There is also a broad range of severity, from quite mild to incapacitating. No specific neuroanatomical or neurochemical basis has yet been discovered, but the basal ganglia and dopaminergic systems have been implicated. Children and adults with TS experience the intrusion into consciousness of unwanted and disturbing sensations, thoughts and desires; they repeatedly experience the need, arising from an "alien" force within themselves, to produce sounds and actions which they try to resist but to which they eventually capitulate. Their symptoms elicit strong responses from family and others, as well as themselves. Psychoanalytically guided, clinical study can help illuminate the inner world of individuals with TS and define the pathways between biological vulnerability and clinical expression. Treatment often requires a combination of approaches, including guidance, psychotherapy and, in a minority of cases, the careful use of medication. Over the past decade, TS has served as a model developmental disorder for studying the interactions between biological vulnerability and environmental responses in the emergence of a clinical disorder and in the shaping of a child's character. During the next years, further advances in the study of TS should help clarify basic issues in the transmission of constitutional vulnerability and suggest approaches to prevention and early intervention.


[Reflections of a child psychiatrist on the diagnosis and hospitalization in psychiatry of adults: an experience of David Rosenhan].

In the 1970s, David Rosenhan and seven other persons were hospitalized in twelve different psychiatric hospitals, pretending having heard voices uttering such words as void, hollow, thud. They were immediately hospitalized with a diagnosis of schizophrenia and, for one of them, of bipolar condition. Right after entering hospital, they reversed to normal behavior. None of them had a psychiatric history. Nevertheless, they were released after a time lapse of 7 to 52 days with a mean of 19 days. Release diagnosis was the same as the admission with the adjunct "in remission". D. Rosenhan points out the contextual and incertain aspect of the diagnosis and underlines the fact that it is apparently impossible to consider as being normal a person who has been admitted to a psychiatric hospital. Psychiatric labels stick to the skin. D. Rosenhan describes the pervasive boredom in a psychiatric hospital and the general set which leads to de-personalization. C. Chiland gives some precisions on what lead D. Rosenhan to undertake such an "experiment". She analyzes the reactions of the American psychiatric community which felt attacked in it's knowledge to the point of entirely rejecting the message. Indeed the criticism concerned the contextual aspect of diagnosis in the framework of the Gestaltpsychology and called to a necessary awareness of what is experienced by a hospitalized patient. Instead of seeking solutions to ward off the negative effects of the psychiatric hospital, effects that are inherent to any total institution, the community has rejected Rosenhan's experiment as being based on faking. Should a child psychiatrist feel securely innocent? The danger of labelling does exist for the children and their parents. Although a one-way choice in the dynamic contradiction between segregation and integration is not possible, one nevertheless has to remain vigilant regarding the institutions, even in day-care ones, so as to avoid imprisoning the child in rejection or stagnation attitudes.