A single dose of dapagliflozin, an SGLT-2 inhibitor, induces higher glycosuria in GCK- and HNF1A-MODY than in type 2 diabetes mellitus.

AIMS: SGLT2 inhibitors are a new class of oral hypoglycemic agents used in type 2 diabetes (T2DM). Their effectiveness in maturity onset diabetes of the young (MODY) is unknown. We aimed to assess the response to a single dose of 10 mg dapagliflozin in patients with Hepatocyte Nuclear Factor 1 Alpha (HNF1A)-MODY, Glucokinase (GCK)-MODY, and type 2 diabetes. METHODS: We examined 14 HNF1A-MODY, 19 GCK-MODY, and 12 type 2 diabetes patients. All studied individuals received a single morning dose of 10 mg of dapagliflozin added to their current therapy of diabetes. To assess the response to dapagliflozin we analyzed change in urinary glucose to creatinine ratio and serum 1,5-Anhydroglucitol (1,5-AG) level. RESULTS: There were only four patients with positive urine glucose before dapagliflozin administration (one with HNF1A-MODY, two with GCK-MODY, and one with T2DM), whereas after SGLT-2 inhibitor use, glycosuria occurred in all studied participants. Considerable changes in mean glucose to creatinine ratio after dapagliflozin administration were observed in all three groups (20.51 ± 12.08, 23.19 ± 8.10, and 9.84 ± 6.68 mmol/mmol for HNF1A-MODY, GCK-MODY, and T2DM, respectively, p < 0.001 for all comparisons). Post-hoc analysis revealed significant differences in mean glucose to creatinine ratio change between type 2 diabetes and each monogenic diabetes in response to dapagliflozin (p = 0.02, p = 0.003 for HNF1-A and GCK MODY, respectively), but not between the two MODY forms (p = 0.7231). Significant change in serum 1,5-AG was noticed only in T2DM and it was -6.57 ± 7.34 mg/ml (p = 0.04). CONCLUSIONS: A single dose of dapagliflozin, an SGLT-2 inhibitor, induces higher glycosuria in GCK- and HNF1A-MODY than in T2DM. Whether flozins are a valid therapeutic option in these forms of MODY requires long-term clinical studies.

Carotid Plaques Correlates in Patients With Familial Hypercholesterolemia.

Patients with familial hypercholesterolemia (FH) are at increased risk of premature cardiovascular disease. We compared factors associated with the presence of carotid plaques and carotid intima-media thickness (cIMT), markers of subclinical atherosclerosis, in 241 patients with FH (98, 40.7% men; mean age 41 ± 18.4 years). Patients with FH having carotid plaques (36.5%) had mean age, apolipoprotein (apo) B, glucose, apoA1, systolic blood pressure (SBP) and diastolic BP, waist/hip ratio (WHR), and body mass index higher than patients without plaques. Logistic regression revealed that apoB (odds ratio [OR] per 1 unit change 1.03,P= .005), high-density lipoprotein cholesterol (HDL-C; OR per 1 standard deviation [SD] change 0.59,P= .015), and non-HDL-C (OR per 1SD change 1.53,P= .04) were significantly associated with the presence of plaques. The cIMT correlated with obesity parameters, BP, apoB, glucose, high-sensitivity C-reactive protein, creatinine, γ-glutamyl transpeptidase, and alanine transaminase (P< .001). Regression analysis revealed that cIMT was significantly associated with apoB, SBP, and WHR. These results confirm the role of apoB-containing lipoproteins and low HDL-C with the presence of carotid plaques and apoB, BP, and WHR with cIMT.

Somatization and depression in fibromyalgia syndrome.

Psychiatric diagnoses, self-reports of symptoms, and illness behavior of 20 fibromyalgia patients and 23 rheumatoid arthritis patients were compared. The fibromyalgia patients were not significantly more likely than the arthritis patients to report depressive symptoms or to receive a lifetime psychiatric diagnosis of major depression. These results do not support the contention that fibromyalgia is a form of somatized depression. Fibromyalgia patients, however, reported significantly more somatic symptoms of obscure origin and exhibited a pattern of reporting more somatic symptoms, multiple surgical procedures, and help seeking that may reflect a process of somatization rather than a discrete psychiatric disorder.

Eye muscle membrane reactive antibodies are not detected in the serum or immunoglobulin fraction of patients with thyroid-associated ophthalmopathy using an ELISA and crude membranes.

We tested sera and purified immunoglobulin (Ig) fractions from patients with autoimmune thyroid disorders (AITD), with and without ophthalmopathy, and normal subjects, for the presence of antibodies reactive with eye muscle membrane antigens in an optimized enzyme-linked immunosorbent assay (ELISA). We found no correlation between ELISA results and the presence or severity of ophthalmopathy in patients with AITD for either serum or Ig, and there were no significant differences between the mean values (+/- SE) for the three groups (AITD with ophthalmopathy, AITD without ophthalmopathy and normals) for either serum or Ig. In contrast Ig from 8 of 19 (45%) patients with thyroid-associated ophthalmopathy reacted with a 64 kDa eye muscle membrane antigen in SDS-polyacrylamide gel electrophoresis and Western blotting, while tests were positive in only one of the 8 patients with AITD without eye disease and in none of the 8 normal subjects. The presence of antibodies to a 64 kDa antigen in immunoblotting did not correlate with the levels of antibodies measured in ELISA. We conclude that the ELISA, incorporating a crude membrane fractions as antigen, is not useful as a clinical test for eye muscle autoantibodies.

Use of the ganciclovir implant in the treatment of recurrent cytomegalovirus retinitis.

OBJECTIVE: To evaluate the efficacy of the ganciclovir implant in the treatment of recurrent cytomegalovirus (CMV) retinitis. METHODS: Patients with acquired immunodeficiency syndrome and recurrent CMV retinitis were evaluated for entry into the study. A ganciclovir implant was inserted in 91 eyes of 70 patients between October 1992 and October 1995. The efficacy of the implant and visual results were retrospectively reviewed. RESULTS: Fifty-three (76%) of 70 eyes had inactive CMV retinitis 1 month postoperatively (positive initial response). Twenty-one eyes of 19 patients had less than 1 month of follow-up. Nineteen (36%) of 53 eyes developed recurrent CMV retinitis. The median time to recurrence for those patients with a positive initial response was 7 months. Forty-eight (84%) of 57 patients with follow-up longer than 1 month after implant insertion in the first eye received systemic anti-CMV medication during the study. The cumulative risk for developing a retinal detachment was 23% at 6 months following implant insertion. Other complications included vitreous hemorrhage, hyphema, and suprachoroidal implantation of the device. CONCLUSION: The ganciclovir implant is effective as an adjunct to continued systemic therapy in those patients with recurrent CMV retinitis.

Traumatic aortic transections: eight-year experience with the "clamp-sew" technique.

BACKGROUND: Because traumatic aortic transection is associated with high mortality rates, great debate exists about the appropriate operative technique for treatment of patients who have acute traumatic aortic transection. METHODS: To determine the safety and efficacy of the "clamp-sew" method, we retrospectively reviewed our 8-year experience treating 75 patients who had aortic injuries secondary to blunt trauma. Seventy-one of these patients were treated surgically. The clamp-sew method was used in all of these operations. RESULTS: Aortic cross-clamp time averaged 24 minutes (range, 14 to 36 minutes), with 4/71 having times in excess of 30 minutes. One patient (clamp time, 28 minutes) became paraplegic. Significant associated injuries were seen in 51/75 patients (48/71 patients with operation), including intrathoracic (35 patients), orthopedic (28 patients), intraabdominal (24 patients), and central nervous system (17 patients) damage. No patient died within 24 hours of operation. Overall 30-day mortality was 12% (9/75), with 7/9 having two or more aforementioned associated injuries. Of these 7, 5 had central nervous system injuries. Two of 9 died within 30 days without two or more associated injuries: 1 Jehovah's Witness of low hemoglobin, and 1 patient of sepsis. CONCLUSIONS: Although any of several maneuvers may be appropriate in managing traumatic aortic injuries, the simple "clamp-sew" technique is a safe and effective method for the treatment of traumatic aortic transections.

Vitritis as the primary manifestation of ocular syphilis in patients with HIV infection.

PURPOSE: To describe dense vitritis as the primary manifestation of ocular syphilis in three human immunodeficiency virus (HIV)-positive patients and to determine the response of these patients to the established regimen for neurosyphilis. METHODS: Anti-Toxoplasma gondii IgM and IgG antibody titers, tuberculin skin test, chest radiograph, and serum angiotensin-converting enzyme level were obtained because tuberculosis, sarcoidosis, and toxoplasmosis were in the differential diagnosis. Two of the three patients were not known to have HIV infection at the time of initial examination and consented to HIV testing. Treponemal and nontreponemal tests were performed on serum and cerebrospinal fluid to establish a definitive diagnosis. Treatment for neurosyphilis was initiated, and daily ophthalmic examinations were performed, with careful attention to signs commonly associated with syphilitic eye disease. RESULTS: All three patients exhibited improvement in visual acuity and resolution of vitreous haze. There was no evidence of other signs of posterior uveitis. The one patient for whom there has been a 6-month follow-up showed no sequelae of his eye disease. CONCLUSIONS: Human immunodeficiency virus-positive patients with syphilis may present atypically dense vitritis. In these patients, vitritis may be the first manifestation of syphilis. The regimen for neurosyphilis provides effective therapy. Moreover, in some patients, syphilitic vitritis may be the initial manifestation of HIV disease.

[Therapeutic and toxicologic aspects of biological effects of Saint John's wort (Hypericum perforatum L.)]. / Terapeutické a toxikologické aspekty biologickej aktivity l'ubovníka bodkovaného (Hypericum perforatum L.).

Saint-John's-wort (Hypericum perforatum L.) has been used in traditional medicine since time immemorial and it has its position also in the contemporary list of medicinal plants of pharmaceutical importance. Though it originally comes from Europe and Asia, it has been domesticated and, thanks to its properties, has been cultivated in many other parts of the world. The herbaceous plant contains a wide spectrum of substances, out of which anthraglycosides, flavonoids, and floroglucin derivatives participate in principal pharmacological effects. In recent years this plant has become greatly popular as an effective alternative means for the treatment of weak to medium forms of depression. Large quantities of mass-produced drugs with its extract are sold mainly in the United States and Germany and successfully penetrate into the markets of other European countries including the Czech Republic. Some adverse side-effects are also connected with the plant, the best known being photosensitivity, lesser known being its interactions with other drugs or foodstuffs. The present review aims to process literary references concerning the biological activities of the plant and point out its most important therapeutic and toxicological aspects.

Ribonuclease in human serum and urine expressed in arbitrary standard units of activity.

A definition of the arbitrary unit expressing the catalytic activity of ribonuclease (RNase) in serum and urine has been proposed. The unit defines the RNase activity solely in terms of a rate of RNase mediated decomposition of RNA-substrate. The proposed unit can be also used for expressing the results of RNase determining in former studies, if their analytical procedures have been enough precisely described. This makes possible the comparison of the recent experimental data with results obtained in other studies carried out with the use employment the nonstandardized RNase determining procedures. In this paper the comparison between the values expressing RNase activity in human serum and urine, published in various studies in years 1965-1992 and recalculated in the proposed arbitrary units, is presented.

[Use of the PCR technique for diagnosis of symptomatic congenital toxoplasmosis based on own observations]. / Zastosowanie techniki PCR w diagnostyce objawowej toksoplazmozy wrodzonej w badaniach wlasnych.

UNLABELLED: The aim of our study was to determine the usefulness of PCR technique in postnatal diagnosis of congenital toxoplasmosis in 17 infants aged from 1 week to 10 months. In 13 cases the diagnosis was established. The diagnostic procedures involved: clinical examinations, serological tests, nested-PCR method and neuroimaging examinations. RESULTS: In almost all children (except one) a high level of toxoplasmatic IgG antibodies was found; in 1/3 we identified antibodies IgM and IgA. In 14 cases the PCR test from CSF was positive. In 4 infants the suspicion of congenital toxoplasmosis was ruled out; in 2 of them PCR from CSF was negative, in 2 - a false positive result was stated. CONCLUSIONS: PCR is a valuable technique for diagnosis of congenital toxoplasmosis. Because of the possibility of false positive and negative results - it should be combined with other laboratory methods.

The virus-activated suppressor cell hypothesis in experimental and human rheumatic diseases.

I suggest that many of the features of the autoimmune diseases may be explained by an alteration in the immunoregulatory balance of various T lymphocyte populations by virus-activated suppressor cells. The evidence for this hypothesis is presented and evaluated in adjuvant disease in rats, NZB/W disease in mice, and in human autoimmune diseases.

Pasteurella multocida arthritis of the shoulder associated with postsurgical lymphedema.

We describe a patient with postsurgical lymphedema and septic arthritis of the shoulder after a cat bite distally. Our case illustrates the importance of a high index of suspicion for infection in patients with shoulder pain and pre-existing edema.

The book of job and the modern view of depression.

The Biblical Book of Job is a wisdom book. Wisdom, in this context, refers to the intellectual discipline taught by the sages of ancient Isreael to provide professionals with a realistic approach to the problems of life. Chapter 30 of the Book of Job is a key-index of ideas that, if followed through the book, discloses a modern scientifically accurate description of a depression that, at times, was life-threatening. There are practical clinical clues to distinguish between normal mourning and depression, as well as aids to the differential diagnosis of somatic symptoms that may arise from depression. A timeless model of the scope and limitations of the professional relation between patient and comforter is also presented. Part of the wisdom of the Book of Job is to use depression as an example of a life-threatening illness to provide an unexcelled standard of clinical observation and medical intervention.

Restoration of diminished T-cell function in adjuvant induced disease by methotrexate: evidence for two populations of splenic T-cell suppressors.

Diminished splenic T-cell function, as measured by their response to phytohemagglutinin and Concanavalin-A, was noted only during the active phase of adjuvant induced disease. This diminished function is due to at least two types of suppressor cell: (a) cells which adhere to glass but not plastic, and which are sensitive to methotrexate in vitro; (b) cells which adhere to plastic and glass, and which are relatively insensitive to methotrexate in vitro. Methotrexate treatment in vivo inhibits adjuvant induced disease, and is associated with the absence of both types of suppressor cells in the spleen.

Outcomes of dropped nucleus during phacoemulsification.

PURPOSE: To evaluate the clinical outcome of vitrectomy in the management of dropped nucleus during phacoemulsification. METHOD: Twenty-five consecutive patients who underwent pars plana vitrectomy for the management of dropped nucleus from phacoemulsification, over a 36-month period, were studied. Twenty-two patients underwent vitrectomy within 15 days of cataract surgery. Most of the patients were followed for more than 6 months. RESULTS: Final visual acuity was 20/40 or better in 71% (17/24) of eyes and 20/50 in 8% (2/24). Visual acuity was 20/70 or worse in 21% (5/24) of patients. Complications included persistent cystoid macular edema in three eyes, epimacular proliferation in two eyes, and a choroidal detachment in one eye. CONCLUSION: Poor visual outcome after dropped nucleus at phacoemulsification cataract extraction can be avoided if managed by prompt pars plana vitrectomy.

The coexistence of rheumatoid arthritis and scleroderma: a case report and review of the literature.

We describe a patient with all the features of the CREST syndrome variant of scleroderma who developed a destructive arthropathy typical of rheumatoid arthritis (RA). A pulmonary rheumatoid nodule was found confirming the presence of RA. The rarity of the coexistence of these two diseases in the same patient suggests that, despite commonly found overlapping features, these illnesses are distinct entities.

Restoration of diminished splenic responses to phytohemagglutinin and concanavalin A in adjuvant-induced disease by corticosteroids: further evidence for the presence and pathogenetic role of two populations of splenic suppressor cells.

This study confirms observations that active adjuvant-induced disease is accompanied by diminished spleen cell responses to phytohemagglutinin and concanavalin A; and that these diminished responses are due to suppressor cells, some adherent only to glass, and others adherent to plastic or glass. Corticosteroid inhibition of adjuvant disease is accompanied by a diminution or absence of these splenic suppressor cells. Some of these suppressor cells are inhibited in vitro by corticosteroids, in preference to the mitogen-responsive cells. This suggests that suppressor cells may play a role in the pathogenesis of AID.

Restoration of diminished splenic responses to phytohemagglutinin and concanavalin A in adjuvant-induced disease by virazole: possible pathogenetic role of a virus and suppressor cells.

Adjuvant arthritis is inhibited by the interferon-inducing anti-viral agents statolon, pyran copolymer and tilorone, and by the passive transfer of interferon. The present experiments demonstrate that Virazole, a non-interferon-inducing, anti-viral agent also inhibits adjuvant arthritis. The responses of splenic lymphocytes to phytohemagglutinin and concanavalin A are diminished in active adjuvant disease, due to suppressor cells. Suppressor cells are absent during spontaneous, methodrexate or corticosteroid-induced remissions. Suppressor cells are also absent during Virazole-induced inhibition of adjuvant disease. Methotrexate and corticosteroids inhibit suppressor cells in preference to mitogen-responsive cells in vitro. The preferential inhibition with Virazole is superior to that noted with methotrexate or corticosteroids.

Illness worry and disability in fibromyalgia syndrome.

Fibromyalgia (FM) is a common syndrome of functional somatic symptoms. This article examines whether an amplifying somatic style (increased body awareness and illness worry) might explain the distress and disability expressed by FM patients. Twenty FM patients were compared to twenty-three rheumatoid arthritis (RA) patients on measures of depressive and somatic symptomatology, pain, disability, and amplifying somatic style. FM patients reported greater somatic symptomatology, equivalent levels of pain, and less physical disability than did RA patients. No differences were observed between groups on body awareness or illness worry. Illness worry correlated highly with symptomatology for both groups but with physical disability only among FM patients. Results suggest that disability in functional somatic syndromes may be determined by patients' worry about having a serious disease. Feelings of vulnerability and apprehension about having an illness of unknown origin may contribute to FM sufferers' activity limitations, inability to sustain a work effort, and varied somatic distress.