Diagnostic approach in lymphoplasmacytic plaque.

BACKGROUND: Lymphoplasmacytic plaque (LPP) is a recently described rare skin disease characterized by a dense dermal lymphohistiocytic infiltrate with polyclonal plasma cells. The clinical picture is distinct with reddish to brownish plaque with a predilection for the lower leg. LPP typically affects children. OBJECTIVE: To define clinical and histologic criteria of LPP and to develop a diagnostic flow chart. METHODS: We investigated six of our own LPP cases. Immunoglobulin light chains, IgG, IgG4, CD31, CD163 as a histiocytic marker were examined by immunohistochemistry. PCR-based molecular studies were conducted for borrelia sp., mycobacterial and leishmania sp. Moreover, 10 cases, which have been reported in the literature, were checked for the same features. RESULTS: We could differentiate three main histological patterns (superficial band-like only, [deep] dermal only and mixed). Acanthosis and interface dermatitis are key features in cases with a superficial band-like or mixed infiltrate. Granulomas and giant cells could be only found in about 30% of the cases. The number of plasma cells was variable accounting for 5-40% of the infiltrate. The number of blood vessels was increased in the majority of the cases. 'Free-floating' collagen bundles surrounded by histiocytes (pseudorosettes) were identified as a new histological feature. An infectious agent could be excluded in all cases. CONCLUSIONS: LPP is a long-standing skin disease, which may also occur in adults and in other body regions than the lower leg. Reproducible clinical and histological criteria allow delineating a diagnostic work-up for LPP.

Nodular morphea.

Scleroderma may present as being strictly limited to the skin, as in morphea, or within a multiorgan disease, as in systemic sclerosis. Accordingly, cutaneous manifestations vary clinically. In nodular or keloidal scleroderma, patients develop lesions that are clinically indistinguishable from a keloid; however, the histopathological findings are more variable. We describe a 16-year-old girl with morpheic lesions for 3-4 years and additional development of keloidal nodules within these lesions. The histological examination revealed a hypertrophic scar besides morphea.

Influence of the pattern of hypertrophy on left ventricular twist in hypertrophic cardiomyopathy.

BACKGROUND/OBJECTIVE: Left ventricular (LV) twist has an important role in LV function. The influence of the pattern of LV hypertrophy on LV twist in hypertrophic cardiomyopathy (HCM) patients is unknown. This study sought to assess LV twist in a large group of HCM patients according to the pattern of LV hypertrophy. METHODS: The final study population consisted of 43 patients with HCM (mean age 43 (15) years, 31 men) and a typical sigmoidal (n = 16) or reverse septal curvature (n = 27) and 43 age-matched and gender-matched healthy control subjects. LV peak systolic rotation (Rot(max)), LV peak systolic twist (Twist(max)) and untwisting at 5%, 10% and 15% of diastole were determined by speckle tracking echocardiography (STE). RESULTS: Compared to control subjects, HCM patients had increased basal Rot(max) (-5.5 degrees (2.3 degrees ) vs -3.4 degrees (1.7 degrees ), p<0.001) and comparable apical Rot(max) (7.3 degrees (3.1 degrees ) vs 7.0 degrees (2.2 degrees ), p = NS), resulting in increased Twist(max) (12.4 degrees (4.0 degrees ) vs 9.9 degrees (2.7 degrees ), p<0.01). Untwisting at 5%, 10% and 15% of diastole was decreased in HCM patients (all p<0.05). There was a striking difference in apical Rot(max )(9.4 degrees (2.8 degrees ) vs 6.0 degrees (2.6 degrees ), p<0.01) and Twist(max) (15.3 degrees (3.2 degrees ) vs 10.6 degrees (3.3 degrees ), p<0.01) between HCM patients with a sigmoidal and reverse septal curvature. CONCLUSIONS: STE may provide novel non-invasive indices to assess LV function in patients with HCM. Apical Rot(max) and Twist(max) in HCM patients are dependent on the pattern of LV hypertrophy.

Potent peptide alpha-ketohydroxamate inhibitors of recombinant human calpain I.

A series of potent dipeptide and tripeptide alpha-ketohydroxamic esters was prepared as inhibitors of recombinant human calpain I. Compound 3c, a Cbz-Leu-Phe hydroxamate, displayed the greatest potency against calpain I (IC(50)=6nM), while two compounds, 3l and 3m, both possessing the Cbz-Leu-Leu-Phe sequence, were the most potent (IC(50)=0.2 microM) in a MOLT-4 cell assay.

(99m)Tc-E-selectin binding peptide for imaging acute osteomyelitis in a novel rat model.

INTRODUCTION: In the present study, (99m)Tc-radiolabelled E-selectin binding peptide ((99m)Tc-IMP-178) was investigated for its potential to image acute pyogenic osteomyelitis in a new animal model. Intraindividual comparisons were performed using an irrelevant peptide ((99m)Tc-IMP-100) to demonstrate specificity. METHODS: An acute pyogenic osteomyelitis was induced by injecting 0.05 ml of 5% sodium morrhuate and 5x10(8) CFU of Staphylococcus aureus into the medullary cavity of the right tibia in 16 rats. Sixteen additional rats served as untreated controls. Whole-body imaging of pyogenic (n=4) and untreated (n=4) animals was performed continuously during the first 8 h (12 MBq i.v. of (99m)Tc-IMP-178 and (99m)Tc-IMP-100 for control), and one further single image was acquired after 16 h p.i. Tissue biodistribution studies were performed in 12 rats with an acute pyogenic osteomyelitis and in 12 untreated rats 1, 4 and 24 h after injection. Data of the histological/radiological and haematological investigations were obtained in all animals. RESULTS: Histopathologically, 15 of 16 treated rats (93%) developed an acute pyogenic osteomyelitis showing a major infiltration of the bone marrow by polymorphonuclear leukocytes as well as the formation of sequestra. Haematologically, the number of leukocytes increased by 100%, the lymphocytes by 11% and the granulocytes decreased by 39%. After i.v. injection, (99m)Tc-IMP-178 rapidly cleared from the body resulting in good scintigraphic target-to-background (T/B) ratios. The highest uptake of the tracer in the pyogenic bone was observed at 60 min p.i. (0.43+/-0.02% ID.g-1 for (99m)Tc-IMP-178 and 0.30+/-0.02% ID.g-1 for (99m)Tc-IMP-100), resulting in a higher osteomyelitis-to-healthy collateral ratio with T/B of 2.40+/-0.65 ((99m)Tc-IMP-178) compared with 1.85+/-0.48 ((99m)Tc-IMP-100). No adverse reactions were seen after injection of (99m)Tc-IMP-178. CONCLUSIONS: (99m)Tc-IMP-178 allows imaging of an acute osteomyelitic lesions, presumably by interaction of (99m)Tc-IMP-178 with activated upregulated vascular endothelium.

PSD-93 knock-out mice reveal that neuronal MAGUKs are not required for development or function of parallel fiber synapses in cerebellum.

Membrane-associated guanylate kinases (MAGUKs) are abundant postsynaptic density (PSD)-95/discs large/zona occludens-1 (PDZ)-containing proteins that can assemble receptors and associated signaling enzymes at sites of cell-cell contact, including synapses. PSD-93, a postsynaptic neuronal MAGUK, has three PDZ domains that can bind to specific ion channels, including NMDA delta2 type glutamate receptors, as well as Shaker and inward rectifier type K(+) channels, and can mediate clustering of these channels in heterologous cells. Genetic analyses of Drosophila show that MAGUKs play critical roles in synaptic development because mutations of discs large disrupt the subsynaptic reticulum and block postsynaptic clustering of Shaker K(+) channels. It is uncertain whether MAGUKs play an essential role in the development of central synapses. There are four neuronal MAGUKs with overlapping expression patterns in the mammalian brain; however, we find PSD-93 is the only MAGUK expressed in cerebellar Purkinje neurons. Therefore, we targeted disruption of PSD-93 in mouse. Despite the absence of MAGUK immunoreactivity in Purkinje neurons from the knock-outs, these mice have no structural or functional abnormality in cerebellum. Both the dendritic architecture and the postsynaptic localization of PSD-93 interacting proteins remain intact at light and electron microscopic levels in the knock-outs. Postsynaptic Purkinje cell responses, monosynaptic climbing fiber innervation, and cerebellar-dependent behaviors are also normal. Our data demonstrate that MAGUK proteins of the PSD-93/95 family are not essential for development of certain central synapses but may instead participate in specialized aspects of synaptic signaling and plasticity.

Further details on sequelae at the cervical and tubal level of Chlamydia trachomatis infection in infertile women.

OBJECTIVE: Relationships were studied between correlates of sexually transmitted diseases and chlamydial antibodies versus cervical mucus abnormalities and tubal abnormalities. An estimate was also attempted of the baseline prevalence of endogenous tubal abnormalities. DESIGN: Prospective, descriptive. SETTING: The outpatient department of the Fertility Unit of the Department of Obstetrics and Gynaecology of the Groningen University Hospital. PATIENTS: Females (n = 184) of infertile couples consecutively visiting the department for evaluation and treatment. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Sexually transmitted disease correlates, cervical chlamydial infection, cervical and serum chlamydial antibodies, cervical mucus qualities according to World Health Organization criteria, tubal abnormalities. RESULTS: Of the 175 cervical mucus samples studied, subnormal quality was because of imperfect timing of collection of 22 of the 23 subnormal samples. Tubal abnormalities correlated with more than five lifetime sexual partners (P less than 0.035), as well as with serum immunoglobulin G antibodies (P less than 0.05), which could be because of interaction between both risk factors. CONCLUSIONS: No correlation was found between subnormal cervical mucus and chlamydial infection. Approximately two thirds of the tubal abnormalities seem unrelated to exogenous factors, although further study seems warranted.

[Chlamydia trachomatis infection in women and the use of oral contraceptives]. / Chlamydia trachomatis-infectie bij de vrouw en het gebruik van orale anticonceptiva.

We determined the prevalence of genital Chlamydia trachomatis infection in women who visited a clinic for sexually transmitted diseases (STD) and the influence of the number of partners and the use of oral contraceptives (OC), with special attention to the recognition of pelvic inflammatory disease (PID) and to the results of therapy. Of 217 women, with a mean age of 26 years (range 14-56), who visited the STD clinic of the University Hospital of Groningen from July 1985 until November 1987, anamnestic data were collected as well as the results of swabs from cervix and urethra taken for culture and direct immunofluorescence test of C. trachomatis and for gonococcal culture. The influence of the number of partners (1 versus greater than 1) and OC on the prevalence of C. trachomatis infection was evaluated by logistic regression analysis. PID was excluded in coöperation with the department of gynaecology. C. trachomatis-infected women were treated by doxycycline orally (day 1 2 x 100 mg, day 2-7 1 x 100 mg) according to the dosage scheme advised by the Dutch Health Council in 1986. A control culture was taken 2-3 weeks after treatment. C. trachomatis was detected in 72/217 (33%) women by culture and (or) direct IF test and in 22/41 (54%) women with gonorrhoea. In connection with the number of partners in the year preceding the examination, the following prevalences were found: 18/74 (24%) (1 partner), 43/108 (40%) (2-5 partners) and 10/27 (greater than 5 partners).(ABSTRACT TRUNCATED AT 250 WORDS)

PIP: The authors determined the prevalence of genital Chlamydia trachomatis infection in women who visited a clinic for sexually transmitted diseases (STDS) and the influences of the number of partners and of the use of oral contraceptives (OCs), with special attention paid to the recognition of pelvic inflammatory disease (PID) and to the results of therapy. Of 217 women with a mean age of 26 years (range 14-56), who visited the STD clinic of the University Hospital of Groningen from July 1985-November 1987, anamnestic data were collected as well as the results from swabs of the cervix and urethra taken for culture and direct immunofluorescence (IF) test of C. trachomatis and for gonococcal culture. The influence of the number of partners (1 vs 1) and OCs on the prevalence of C. trachomatis infection was evaluated by logistic regression analysis. PID was excluded in cooperation with the department of gynecology. C. trachomatis-infected women were treated by doxycycline orally (day 1, 2x 100 mg, days 2-7, 1x 100 mg) according to the dosage scheme advised by the Dutch Health Council in 1986. A control culture was taken 2-3 weeks after treatment. C. trachomatis was detected in 72/217 (33%) of the women by culture and/or direct IF test and in 22/41 (54%) women with gonorrhea. In connection with the number of partners in the year preceding the examination, the following prevalences were found: 18/74 (24%, 1 partner), 43/108 (40%, 2-5 partners), and 10/27 (5 partners). The prevalence among OC-using women was significantly higher (p0.05) than in non-OC using women: 44.101 (44%) vs 21/93 (23%). This was also true when OC users were compared to sterilized women (9/47, 19%), regardless of number of partners and age. Active PID was found in 2 women, both infected. After treatment with positive C. trachomatis cultures, control cultures were negative in 39/40 (98%). A relatively high prevalence of genital C. trachomatis infection is found in women visiting STD clinics, as well as in women with only 1 partner during the year preceding the examination. This study supports the hypothesis of OC use being a risk factor. How OC use influences PID risk is not fully understood. Within the framework of reliable contraception and prevention of STD complications, the combination of OC + a barrier method should be advised to women without a steady partner. Further study is necessary to determine whether preventive antibiotic treatment of asymptomatic adolescents with anamnestic risk factors for C. trachomatis infection is indicated at the start of a new relationship. (author's modified)

[Chlamydia trachomatis diagnosis in women: the value of serological studies and of culture of cervical and urethral swabs]. / Chlamydia trachomatis-diagnostiek bij de vrouw: de waarde van serologisch onderzoek en van kweek van materiaal uit cervix en urethra.

We studied the value of the determination of the serum IgM antibody level for the diagnosis of genital Chlamydia trachomatis infection in women and the value of the urethra in addition to the cervix as a sampling site for the diagnosis of C. trachomatis infection by culture and direct immune-fluorescence (IF) test. Of 205 women, mean age 26 years (range 14-56), who visited the Sexually Transmitted Disease clinic of the University Hospital Groningen from July 1985 until November 1987, single serum samples were obtained for the determination of IgM and IgG anti-C. trachomatis antibodies using FITC conjugates, in addition to swabs of cervix and urethra for culture and direct IF test. In women with a negative culture and positive IgM serology the culture was repeated. The culture was used as golden standard. In 17/205 (36%) women positive C. trachomatis IgM serology (greater than or equal to 1:32) and in 190/205 (93%) positive IgG serology (greater than or equal to 1:40) was found. In 67/205 (33%) women the C. trachomatis culture of cervix and (or) urethra was positive. The positive and negative predictive values of C. trachomatis IgM serology were 41% and 72%. In 3/20 women with negative culture results and positive IgM serology a second culture was positive. In 176 women, of whom samples from both cervix and urethra were available, the only C. trachomatis positive site by culture was the urethra in 7/54 (13%) and by direct IF in 3/42 (7%). The increase in the prevalence obtained by collecting material not only from the cervix but also from the urethra was 4% by culture and 2% by direct IF.2+n

Vaginal hysterectomy: cefuroxime, metronidazole or both?

A randomized double-blind prospective study on the efficacy of single-dose antibiotic prophylaxis compared cefuroxime versus metronidazole versus the combination of both agents in vaginal hysterectomy. Overall antibiotic prophylaxis was effective in abscess prevention (one abscess in 68 patients). In the metronidazole group a significantly higher grade of morbidity was observed: febrile morbidity 41% versus 4% in the two other groups; bacteriuria 73% versus 17% in the cefuroxime group, versus 13% in the combined group; urinary tract infection 23%, versus 0% in the two other groups; post-operative prescription of antibiotics 41%, versus 0% in the two other groups. Febrile morbidity and bacteriuria correlated positively with Escherichia coli and Proteus spp. These micro-organisms were recovered significantly more often from the vagina of patients in the metronidazole group. Cefuroxime was successful, metronidazole failed in the prevention of minor morbidity. We could not observe any effect from the addition of metronidazole to the cefuroxime prophylaxis.

Epidemiological aspects of chlamydial infections and tubal abnormalities in infertile couples.

Demographic and behavioural data on parameters of previous sexual behaviour were collected of both partners of 184 couples visiting the Department of Obstetrics and Gynaecology because of infertility. They were also screened for urogenital infection with Chlamydia trachomatis. Of 131 (71.2%) women, a diagnosis was established by hysterosalpingography and/or laparoscopy about the condition of their fallopian tubes. An unmarried status correlated significantly with a history of sexually transmitted disease, and with past promiscuity of male and female partner. Abnormalities of the fallopian tubes were significantly related to an unmarried status, a history of pelvic inflammatory disease, and past promiscuity. Male promiscuity was not shown to correlate with tubal abnormalities in the female partner. In only three couples, the partners reported to have had a sexual relationship with a partner other than the current one over the past year. The percentage of Chlamydia trachomatis-positive women of 1.8 and men of 3.0 in our study agrees with this low recent promiscuity. Chlamydia trachomatis was shown to be able to maintain itself for at least 4 years within a couple. The results are commented on.

Is serology of any use when searching for correlations between Chlamydia trachomatis infection and male infertility?

Evidence on Chlamydia trachomatis causing male infertility is conflicting. We therefore collected data on epidemiological and clinical correlates of chlamydial infection and male fertility in 184 males visiting our Fertility Unit. Antibodies against Chlamydia trachomatis in serum and semen were also determined. Significant correlations were demonstrated between current chlamydial urethral infection and semen immunoglobulin (Ig) A, serum IgA and serum IgG. These parameters, however, were neither related to a history of sexually transmitted disease nor to lifetime number of sexual partners. Why, in the male, serology does not correlate with chlamydial infection in a more remote past is explained. Our data support, on epidemiological as well as serological grounds, the conclusion that chlamydial infection probably does not contribute significantly to male infertility.

Endometriosis: treatment with gonadotropin-releasing hormone agonist Buserelin.

Fifty-one women with pelvic endometriosis were treated with the gonadotropin-releasing hormone agonist (GnRHa) Buserelin (Hoechst Holland N.V., Amsterdam, The Netherlands) 300 micrograms three times a day intranasally for 6 months. Forty-nine women completed treatment; 42 were available for 6 months of follow-up following treatment. Symptoms showed prompt and significant improvement. Follow-up after treatment revealed persistent relief from dysmenorrhea and dyspareunia in, respectively, 58.6% and 88.2% of the women, whereas pelvic pain returned to pretreatment scores. Serum estradiol (E2) was suppressed to predominantly early follicular phase concentrations. Laparoscopy at the end of therapy showed significant reduction of scores for implants only. There was no relation between the degree of E2 suppression during therapy and the improvement of symptoms or the reduction of endometriosis. Statistical analysis in 22 infertile patients, of whom 7 conceived during follow-up, revealed no differences in E2 levels during therapy, improvement of symptoms, or reduction of endometriosis. Buserelin appears to be safe, well tolerated, and effective in the management of endometriosis and associated complaints.

Serum CA 125 levels in patients with a provisional diagnosis of pelvic inflammatory disease. Clinical and theoretical implications.

In 50 patients with a provisional diagnosis of pelvic inflammatory disease (PID), CA 125 concentrations in serum were measured before laparoscopy and during hospitalization, using an enzyme immunoassay. The findings at laparoscopy were graded on the basis of the extent of inflammatory peritoneal involvement (grades 0-3; normal observations having a score of 0). On admission, 66% of the patients had serum CA 125 concentrations in excess of the cut-off value of 16 U/ml (range: 20-1300 U/ml). The serum CA 125 concentration before laparoscopy correlated with the extent of inflammatory peritoneal involvement (eta = 0.74). The predictive value of an elevated serum CA 125 level to indicate the presence of salpingitis (grades 1-3) was 97%. However, the predictive value of a normal CA 125 level indicating normal observations at laparoscopy (grade 0) was only 47%. During treatment and follow-up, the serum CA 125 concentration returned gradually to normal levels. It was concluded that the finding of an elevated serum CA 125 level confirms the diagnosis of peritoneal involvement in patients with a clinical diagnosis of PID.

Direct immunofluorescence for Chlamydia trachomatis on urogenital smears for epidemiological purposes.

A population of 197 asymptomatic women, attending an out-patient department for birth-control advice, was screened for urogenital infection with Chlamydia trachomatis by direct immunofluorescence on cervical and urethral smears. A blood sample was obtained for chlamydial serology and demographic, behavioural and clinical data were recorded. Eleven (5.5%) women had a chlamydial infection. Chlamydial infection, as diagnosed with direct immunofluorescence, correlated with a history of sexually transmitted disease (p less than 0.01), promiscuity (p less than 0.01), use of oral contraceptives (p less than 0.02) and high chlamydial antibody titres (p less than 0.01). These last also correlated with a history of sexually transmitted disease (p less than 0.02) and promiscuity (p less than 0.02). These results, obtained with direct immunofluorescence, are indistinguishable from those obtained previously with chlamydial culture. Direct immunofluorescence on urogenital smears seems a valuable tool for epidemiological investigation. Our data also support the hypothesis that oral contraceptive use is correlated with chlamydial infection because of increased cervical susceptibility to infection and not because of a sampling bias towards oral contraceptive users.

Antibiotics and suction drainage as prophylaxis in vaginal and abdominal hysterectomy.

A randomized prospective study compared the efficacy of a three-dose perioperative course of intravenously administered cefuroxime and metronidazole versus suction drainage of the vaginal vault for preventing postoperative infection in abdominal and vaginal hysterectomies. In vaginally operated patients, a significant difference in the rate of vaginal cuff abscess formation was found between the drain group and the antibiotic group (33 versus 0%). In the abdominally operated patients, no significant difference was found (7 versus 0%). The rate of cystitis was not influenced by the prophylactic method. A positive correlation was found between Bacteroides sp isolated from the vaginal fluid and vaginal cuff abscesses in the vaginally operated women. The complications of infection are explained by the decrease in host defense, occurring more frequently in patients treated with the vaginal approach than with the abdominal technique.