Borderline Forms Research Articles

Single lesion multibacillary leprosy, a treatment enigma: a case report

IntroductionLeprosy exhibits a wide spectrum of presentation, varying from the tuberculoid to the lepromatous pole, with immunologically unstable borderline forms in-between, depending upon the immune status of the individual. The clinical system of classification for the purpose of treatment includes the number of skin lesions and nerves involved as the basis for classifying the patients into multibacillary and paucibacillary.Case presentationA 20-year-old man belonging to a moderately endemic leprosy area in the Terai region of Nepal reported a large single, hypopigmented, well defined anaesthetic lesion on his left thigh extending to his knee which had been present for 2 years. There was no other nerve involvement. Clinical diagnosis was tuberculoid leprosy and immunological lateral flow test for anti-Phenolic glycolipid-I antibody was positive. Six months of paucibacillary multidrug treatment was advised immediately. However, the patient was reclassified as multibacillary on the basis of a positive skin smear and appropriate treatment of 24 months multibacillary multidrug regimen was commenced after only 1 week. Slit skin smear examination for Mycobacterium leprae from the lesion revealed a bacterial index of 4+ while it was negative from the routine sites. Histopathological examination from skin biopsy of the lesion further supported the bacterial index of the lesion granuloma which was 2+ and the patient was diagnosed as borderline tuberculoid. Bacteriological, histological, and immunological findings of this patient were borderline tuberculoid leprosy and he should have been treated with multibacillary regimen from the beginning. Five months after commencement of treatment, the patient developed a leprae reaction of Type 1 or reversal reaction with some nerve function impairment and enlargement of the lateral popliteal nerve of the left leg. This reversal reaction was managed by standard oral prednisolone whilst continuing the multibacillary multidrug regimen.ConclusionThis case illustrates and emphasizes the importance of slit-skin smear and biopsy as routine in all new cases to help differentiate multibacillary from paucibacillary for correct treatment. It further suggests that there are factors yet undetermined which play a significant role in determining the host response to M. leprae which is a remaining challenge in this disease.

The Association between Mannan‐Binding Lectin Gene Polymorphism and Clinical Leprosy: New Insight into an Old Paradigm

Mannan-binding lectin (MBL), a soluble protein of innate immunity, is known to play a role in pathogen recognition and clearance. For more than a decade, it has been proposed that MBL deficiency may be protective against intracellular pathogens, such as Mycobacterium leprae. The polymorphisms at the promoter and exon 1 regions of the MBL2 gene were assessed by polymerase chain reaction and sequencing performed on 264 patients with leprosy and 214 matched healthy control subjects from southern Brazil. RESULTS. The distribution of MBL2-gene polymorphisms in patients was significantly different from that in controls, with a decreased frequency of haplotypes/genotypes associated with low expression of circulating MBL in lepromatous patients when compared with tuberculoid patients (odds ratio [OR] for haplotypes, 0.56 [95% confidence interval {CI}, 0.33-0.93] [P=.020]; OR for genotypes, 0.31 [95% CI, 0.13-0.71] [P=.004]). The LYPA haplotype was associated with susceptibility to leprosy per se (OR, 2.25 [95% CI, 1.31-3.88] [P=.003]) and to progression to the lepromatous (OR, 2.2 [95% CI, 1.21-4.05] [P=.008]) and borderline (OR, 2.98 [95% CI, 1.29-6.87] [P=.008]) forms of the disease. These results suggest that MBL2-gene polymorphisms play a role in susceptibility to leprosy per se and in the clinical progression of the disease.

Sclérose en plaques : aspects cliniques, encéphalomyélites aiguës disséminées, neuromyélites optiques et variantes inflammatoires

Multiple sclerosis (MS) has been described for more than a century, but its cause remains unknown. Numerous reports were written concerning borderline forms of the disease. In the present review we present MS related disorders such as neuromyelitis optica and acute demyelinating encephalomyelitis.

Leprosy-specific B-cells within cellular infiltrates in active leprosy lesions

Leprosy is a spectral disease with polar lepromatous and tuberculoid forms correlating with enhanced humoral and cell-mediated immunity, respectively, against Mycobacterium leprae and the borderline forms, borderline lepromatous, midborderline, and borderline tuberculoid showing in-between clinical and immunological characteristics. Histopathologically, the cellular infiltrates of leprosy lesions show predominantly the presence of interacting T-cells and antigen presenting cells like macrophages, whereas the presence of B-cells has only been sporadically reported. The present study demonstrates by immunohistochemical techniques the presence of B-cells, including plasma cells, in active lesions from lepromatous leprosy, skin smear negative borderline lepromatous, and paucibacillary borderline tuberculoid leprosy. Furthermore, the study demonstrates the in situ production of M leprae-specific antibodies from BT lesions using an organotypic skin explant culture model. Finally, analysis of the cytokine release profile in supernatants of lesional organotypic skin cultures showed a microenvironment conducive to the differentiation and maturation of B-cells. The results demonstrate the presence of different functionally active B-cell stages within lesions of patients with leprosy, including borderline tuberculoid patients, which could secrete anti-M leprae-specific antibodies. However, their role in leprosy pathology remains to be elucidated.

Surgical methods for the treatment of breast phylodes tumors - a report of 319 cases

Breast phyllodes tumors (FT) belong the fibroapitelial group of breast tumors arising in terminal ductulo-lobular unit (TDLU). Their incidence do not exceed 1% of all breast tumors. Biologicaly they can be divided into benign, borderline and malignant group. Incomplete tumor excision can be the reason for local reccurence. Malignant form of FT metastazise hematogenous most often in the lung. There is no uniform surgical opinion about the treatment FT. We analyzed histopathology features of 319 FT of the breast surgicaly removed on Departement of surgery Institut of oncology and radiology of Serbia between 1.1.1985.-31.12.1994. Retrospective study of surgical treatment 84 patients with FT of the breast (69 benign, 4 borderline and 11 malignant) and 5 year follow up after surgery we analysed. local reccurence after surgery was found in 17 (20,2 %) patients(14 benign , 2 borderline and 1 malignant FT), pulmonary metastases in 6 (7,1%) patients with malignant FT. DFI was 21,3 months for local reccurences and 25,1 months for pulmonary metastases. DFS for al forms of FT was 71 % (p =0,7104) in 5-year follow up. According to biological behavior we propose wide excision for benign and borderline forms and simple mastectomy for malignant FT, and voluminous benign and borderline forms. Axillary disection is not necessary because lymphatic spread of malignant FT is unfrequent.

Congenital hypothyroidism with gland in situ: Diagnostic re-evaluation

In the past, most congenital hypothyroidism (CH) children with thyroid gland in situ were considered to be affected by hormonogenesis defect. Nowadays, the improved sensitivity of neonatal screening, novel insights into the pathogenic mechanisms and the advances of genetic analyses have reopened the discussion about the etiology of CH with thyroid in situ. We report the etiological re-evaluation of 31 children with thyroid in situ, who had been identified by the CH screening program. The purposes of this re-evaluation were: a) to investigate the definitive diagnosis and pathogenetic mechanism of CH with thyroid in situ in eligible children suspected of dyshormonogenetic defect and b) to verify the adequacy of the treatment schedules. Thirty out of 31 children were affected with permanent hypothyroidism and only one child was euthyroid at re-evaluation (transient CH). Thyroid hormone organification defects were present in less than half of the CH patients with thyroid in situ (13/30); a higher prevalence of partial defects of iodine organification than severe or complete forms was found. An inactivating TSH-receptor gene mutation was found in only one patient without iodine organification defect. Some questions remain unanswered concerning the adequacy of the schedules of treatment, particularly about the proper treatment of mild and borderline forms of CH.

Width of the fetal lateral ventricular atrium between 10 and 12 mm: a simple variation of the norm?

The prognosis of borderline forms of anomalies that can be detected by ultrasound is one of the most challenging issues in prenatal diagnosis. The aim of this study was to determine the prognosis for fetuses presenting with isolated mild ventriculomegaly (MVM). Fetuses in which the width of the lateral ventricular atria was 10-12 mm and which had no other detectable chromosomal or morphological anomalies were followed by monthly ultrasound examinations until delivery. For the cases identified up to December 1997, postnatal information was gathered retrospectively through interviews. Children born from January 1998 onwards were included in a protocol involving planned neuropsychiatric visits at 12 and 18 months of age in which the Griffith scale was used to assess neurodevelopment. Between September 1992 and January 2001, 60 fetuses with isolated MVM were identified. Ventricular dilatation diminished in 18 cases (and became normal in nine of these) and stabilized in 42 cases. Information was obtained on 38 children born up to December 1997 and their neurodevelopment was found to be completely normal. The 22 children born from January 1998 onwards showed normal development at 12 and 18 months of age. When MVM is observed on prenatal ultrasound examination it can be very difficult to offer parents appropriate counseling. It is important to exclude aneuploidy or morphological abnormalities but even then there will be anxieties about long-term neurological outcome. Our data, which show normal neurodevelopment between 18 months and 10 years after birth in cases of MVM (10-12 mm), should provide a basis for reassuring counseling.

Loss of heterozygosity on chromosomes 7p, 7q, 9p and 11q is an early event in ovarian tumorigenesis.

Forty early stage malignant and seven borderline ovarian tumours were analysed for loss of heterozygosity (LOH) on chromosomes 6, 7, 9, 11 and 17. LOH involving at least one locus was observed in 32 (80%) early stage and six (86%) borderline tumours. Frequent LOH in the early stage tumours was detected on chromosome arms 7p (31%), 7q (50%), 9p (42%) and 11q (34%) suggesting that these chromosomes harbour tumour suppressor genes which are inactivated early in tumorigenesis. Borderline tumours exhibited a similar pattern of LOH to that observed in the early stage malignant tumours, indicating that the development of both malignant and borderline forms may involve inactivation of the same set of tumour suppressor genes. Together with our previous investigation of benign ovarian tumours this data supports the theory that malignant ovarian tumours may arise from benign and borderline precursors.

Diastolic pressure underestimates age-related hemodynamic impairment.

It has been hypothesized that as large arteries become more rigid with age, the pattern of hypertension changes from diastolic to systolic. Thus, diastolic blood pressure (DBP) may lose its ability to reflect the increase in vascular resistance with age. To assess this, we studied the age-related changes in blood pressure pattern and its steady-state and pulsatile determinants. We performed an epidemiological analysis based on a national survey of 10,462 subjects from Argentina. A hemodynamic analysis (impedance cardiography) was then carried out in 636 consecutive hypertensive patients (age, 25 to 74 years). Whereas the rate of increment in the prevalence of mild to moderate hypertension (MMH) reached a plateau after the sixth decade, isolated and borderline systolic forms of hypertension began a steep and sustained rise. Among patients with MMH, DBP remained stable from the third to the seventh decade, whereas SBP maintained a sustained increase. Despite similar DBP, the systemic vascular resistance index increased 47% (P<.01) and the cardiac index decreased 27% (P<.01), whereas the ratio of stroke volume to pulse pressure, an index of arterial compliance, decreased 45% (P<.01). However, there were no significant differences between older patients with MMH and those with isolated systolic hypertension in the level of SBP, vascular resistance, stroke volume, and cardiac index. Compared with age-matched normotensive control subjects, the ratio of stroke volume to pulse pressure was much more reduced in isolated systolic hypertension (48%) than in MMH (30%). In summary, the present study, carried out in a large sample of hypertensive subjects with a wide age range, showed a simultaneous impairment in vascular resistance and arterial compliance associated with aging in different patterns of hypertension. The magnitude of these changes, with opposite effects on DBP but additive effects on SBP, suggests that a hemodynamic mechanism could determine the transition in the prevalence of diastolic hypertension toward a systolic pattern of hypertension with aging. Also, the results suggest that SBP, but not DBP, is a reliable indicator of the underlying hemodynamic abnormalities (high resistance and low arterial compliance) in the elderly.

Role of fine-needle aspiration cytology in the preoperative evaluation of smooth muscle tumors.

A preliminary study was undertaken to assess the feasibility and the diagnostic role of fine-needle aspiration cytology (FNAC) in the preoperative evaluation of eight uterine smooth muscle tumors manifesting as single large masses with signs of growth. Percutaneous FNAC was performed under echographic control with a 22-gauge needle and the material was stained according to conventional techniques. Histology of surgically resected specimens was available for final diagnosis and comparative analysis in all the cases, including five leiomyomas (LM), one smooth muscle tumor of uncertain malignant potential (TUMP), and two low-grade leiomyosarcomas (LMS). Cellularity, as indicated by the density (crowding) of nuclei reflecting the amount of cytoplasmic volume, and the cohesiveness of the tissue fragments in the smears appeared to be the most important diagnostic parameters in the distinction between LM and LMS. LM usually showed few scattered poorly cellular fragments of highly cohesive tapering cells without nuclear crowding and with abundant cytoplasm. LMS usually showed a large number of single cells and fragments of loosely arranged tapering cells with nuclear enlargement and crowding and ill-defined scanty cytoplasm. Borderline forms such as TUMP were hardly distinguishable from LMS and LM. FNAC appears to be a feasible preoperative procedure in uterine smooth muscle tumors and may play a diagnostic role, especially in distinguishing frankly benign from overtly malignant forms.

Novel responses of human skin to intradermal recombinant granulocyte/macrophage-colony-stimulating factor: Langerhans cell recruitment, keratinocyte growth, and enhanced wound healing.

Recombinant granulocyte/macrophage-colony-stimulating factor (rGM-CSF), prepared from Chinese hamster ovary (CHO) cells and Escherichia coli, was administered to 35 patients with the borderline and polar lepromatous forms of leprosy by the intradermal and subcutaneous routes at doses of 7.5-45.0 micrograms/d for 10 d. With each of these doses and routes, increases in the number of circulating eosinophils were noted. After the intradermal injection, the local skin sites demonstrated zones of roughening and micronodularity that appeared within 24-48 h and persisted for more than 6 d. Reinjection of sites led to enhanced areas of epidermal reaction. GM-CSF prepared from CHO cells was a more potent inducer of this effect. GM-CSF given by the subcutaneous route, at higher doses, failed to initiate these changes. At the microscopic level, the epidermis became thickened (+75%) with increased numbers and layers of enlarged keratinocytes. These contained increased numbers of ribosomes and prominent nucleoli, and were imbedded in a looser meshwork of the zona Pellucida. The modified keratinocytes remained MHC class II antigen negative throughout the course of the response. A major change in the dermis was the progressive accumulation of CD1+, Birbeck granule-positive cells. These Langerhans were recognizable at 48 h after intradermal injection and reached maximum numbers by 4 d. During this period the number of epidermal Langerhans cells remained relatively constant. No increment in dermal Langerhans cells occurred when GLM-CSF was injected by the subcutaneous route. No appreciable increase in the numbers of T cells and monocytes was noted, and granulocytes and eosinophils were largely present within the dermal microvasculature. 4-mm punch biopsies taken from injected sites and adjacent controls were compared in terms of the rapidity of wound healing. 22 of 26 sites demonstrated more rapid filling and hemostasis, whereas four were equivalent to controls. We conclude that rGM-CSF, when introduced into the skin, leads to enhanced keratinocyte growth, the selective recruitment of Langerhans cells into the dermis, and enhanced wound healing of the prepared site. There was no evidence of an enhanced cell-mediated response to Mycobacterium leprae, and bacillary numbers remained unchanged.

Electromyographic diagnosis of leprosy

Eighty untreated patients suspected to have leprosy were submitted to neurophysiological examination and later compared with the clinical diagnosis. Among the patients who had leprosy confirmed, 98% had EMG abnormalities. Motor and sensory amplitude reduction was the earliest and the most frequent abnormality. Low conduction velocity of the ulnar nerve across the elbow was present in over 55% of the patients. A "mosaic" peripheral polyneuropathy was the most characteristic finding, and seems to be helpful to the diagnosis of leprosy. All of the clinical forms showed EMG abnormalities, and even some asymptomatic contacts, however the abnormalities increase from the undetermined and tuberculous to the borderline and Virchow's forms.

Research on the Clinical Usefulness of the Rorschach: 1. The Diagnosis of Schizophrenia

Research on the use of the Rorschach in the diagnosis of schizophrenia is reviewed. The analysis of this research (from that done by Rorschach to the most recent) indicates that schizophrenics do not respond in any unique fashion to any particular determinant or any particular card. The research also indicates that the computation of percentages and ratios, no matter how complex, does not facilitate the identification of a schizophrenic process. What the research does demonstrate is that schizophrenia, in its overt as well as latent and borderline forms, is detectable on the Rorschach through an analysis of the patient's thinking. The thinking of the schizophrenic reveals highly personal, illogical, and bizarre associations to the blots. This analysis of thinking is not accomplished through assessment of the formal properties of the blots, e.g., the analysis of response to color, movement, shading, the color-to-movement ratio, or form level (low form level proves to be a function of psychoticism, not schizophrenia, per se) but more in terms of the phenomenology of the responses.

A induction of the late hipersensitivity reaction to DNCB in patients with different clinical forms of hanseniasis in Brazil

One hundred and twenty Brazilian patients with several forms of hanseniasis were tested with DNCB. The results were the following: 1) the sensitization of patients with hanseniasis to DNCB was lower than that seen in the general population; 2) the sensitization of the borderline and virchowian forms of hanseniasis were lower than that seen In the indeterminate and tuberculoid forms.

Gamma interferon production induced by antigens in patients with leprosy and American cutaneous leishmaniasis.

In this study, we measured gamma interferon production in mononuclear cell cultures from patients with diverse forms of leprosy and American cutaneous leishmaniasis. We studied patients with lepromatous, borderline lepromatous, borderline, and borderline tuberculoid forms of leprosy, as well as a Mitsuda-negative contact. In leishmaniasis we studied patients with localized cutaneous, mucocutaneous, and diffuse cutaneous forms of the disease. High correlation was observed between gamma interferon production and lymphocyte proliferation assays in both diseases. Resistant forms of both diseases showed significant reactivity, while the severe progressive forms were characterized by insignificant responses in both assays. Localized cutaneous leishmaniasis is characterized by variability in gamma interferon production, which may be of prognostic value in longitudinal studies.

Serum Macrophage Migration Inhibition Activity in Patients with Leprosy

We have found that 26 of 54 (48%) untreated patients with leprosy had serum migration inhibitory activity, and that this was present in tuberculoid, borderline, and lepromatous forms of the disease. Patients with active recreational states; i.e., reversal reactions, Lucio's reaction, or erythema nodosum leprosum, were particularly apt to have this inhibitory activity. The prevalence of inhibitory activity did not vary significantly with treatment, dinitrochlorobenzene responsiveness, tuberculin responsiveness, or serum lysozyme levels.

Pharmacotherapy with psychotropic drugs

From 6 to 12% of the population of economically developed countries suffer from various mental disorders, more than 80% of which are borderline forms of neuropsychic pathology [2]. These include those psychopathological conditions that are manifested by symptoms of anxiety and fear, increased fatigue and exhaustion, increased irritability, anxious suspiciousness, low mood, obsessions, senestopathies, hypochondria, insomnia, autonomic disorders. These mental disorders are observed both in mental illnesses - neuroses, psychopathies, sluggish schizophrenia, and in neurosis-like and psychopathic conditions arising from somatic diseases [12]. The pathogenesis of borderline states has not been fully studied, but the fundamental idea that psychogenic (sociogenic) and biological (constitutional, genetic, 'exogenous) factors are combined in their origin in a dialectical unity has been established in Russian literature. It is generally accepted that the treatment of patients with borderline conditions should be comprehensive - to combine psycho- and pharmacotherapy [2, 3]. Psychotherapy addresses the psychogenic links of pathogenesis, pharmacotherapy - to biological ones.

A System of Treatment and Rehabilitation of Hyperactive Children

Many years of coping with hyperactive behavior in children have confronted researchers with ever new problems to solve. As early as the 1920s, Soviet child psychiatrists (M. O. Gurevich, 1927; V. P. Kashchenko, 1919; T. P. Simson, 1929; and M. I. Jogikhes, 1929) endeavored to show that hyperactivity was not just a medical or just a pedagogical problem, but a combination of both. In 1919 a psychoneurological sanatorium school was established for nearnormal children from the ages of 8 to 14 with minor aberrations in the sense of nervousness and general neurological imbalance (M.O. Gurevich, 1925). In many countries the 1950s were marked by growing concern about hyperactivity in children, and later this problem became one of the leading and most debated questions in child psychiatry. There were, of course, a number of circumstances that contributed to this development: 1. Serious exogenous organic mental disorders had decreased in frequency, and borderline forms of psychiatric disturbances had gained significance. 2. Improvements in obstetric techniques had considerably reduced perinatal infant mortality and increased the survival rate of children with perinatal damage of the nervous system. 3 . The growing socialization and urbanization of society that followed in the wake of the qualitative progress brought about by the scientific and technological revolution meant that formal schooling and instruction had become the foundation on which any later coop-

Occult Spinal Dysraphism: A Series of 73 Cases

The subject of occult spinal dysraphism or myelodysplasia is reviewed from standpoints of embryology, clinical manifestations, and treatment, and the management of 73 cases summarized. In general, these concealed lesions arise from developmental variants in the most distal part of the neural tube, a situation which may cause distortion or partial absence of neural tissues and also lead to damage from compression or traction. Lipomyelomeningocele and congenital dermal sinus are two exampled of the many types of such lesions, but some are more complicated and border-line myelomeningocele-like forms occur. Incontinence, deformity or weakness of the feet, impaired gait, and other difficulties may appear late and increase with growth. Surgical treatment is advised to reduce chances of delayed or progressive loss of function.

The genus Candida Berkhout. 8. Fermentation Type II species.

The properties of 53 fermentation type II strains of the genusCandida Berkhout were studied. The strains in question were originally identified asCandida tropicalis (Castellani) Berkhout,Candida pelliculosa Redaelli,Candida robusta Diddens et Lodder,Candida intermedia (Cif. et Ashf.) Langeron et Guerra,Candida langeroni Dietrichson,Candida obtusa (Dietrichson) v. Uden et Carmo Sousa and as various intermediate forms between these and other similar species. The classification criteria were extended by a number of very important characteristics, such as the degree of utilization of raffinose, the assimilation of lysine, xylose, cellobiose, maltotriose, maltotetraose and arabinose, virulence for mice, nutrient requirements, serological properties, etc. Actual classification was based on the numerical method of a similarity count. On the basis of this extension of the classification criteria, the characteristics of the speciesCandida tropicalis (Castellani) Berkhout andCandida pelliculosa Redaelli were defined in greater detail.Candida intermedia, evaluated on the basis of previously employed characteristics (lactose utilization, non-assimilation of KNO3) does not appear to be a separate species, but a collection of different border-line forms of other species of this group.Candida robusta Diddens et Lodder is regarded as a member of the genusSaccharomyces, notCandida. The varietiesCandida tropicalis var.lambica andCandida pelliculosa var.cylindrica likewise do not seem to belong to the species concerned and will have to be studied in greater detail from the genetic aspect, in relation to other membrane-forming types ofCandida.